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There are, quite often, cases of poisoning of human population with poor-quality alcoholic drinks, which include methanol. The optic nerve, retina and brain tissues are initially affected. A long-term study aimed at identifying initial structural changes in the visual analyzer in the application of various doses of methanol and its mixture with ethanol was carried out. Purpose: to study the dynamics of ultrastructural changes in glial cells and nerve fibers of the optic nerve, which are caused by mixture of ethanol 40% and methanol 100% in a ratio of 3:1 with a dose of methanol of 0.75 g/kg of rat weight. We examined the ultrastructure of the orbit part of the optic nerve of 43 adult rats (Wistar line) in the period from 3 hours to 14 days after one-time intra-abdominal injection of ethanol 40% and methanol 100%, 100% methanol, the dose of methanol is 0.75 g/kg of rat weight. In rats, LD50 is 9.5 g/kg of their weight. It was found out, that within 3 hours after the injection of the mixture of alcohols, the myelin sheath of large-caliber nerve fibers exfoliated, the axoplasm swelled and the mitochondria in their axons pathologically changed, the mitochondria altered in glial cells, which influenced the quality of nerve impulses and axoplasmic transport of substances. In the dynamics of the study, alterative changes in structures of the optic nerve progressed with the complete destruction of part of glial cells by 7 days, mainly in the first 3 days. After the use of methanol 100%, changes in structures of the optic nerve were similar to changes in them after the use of a mixture of alcohols, but with more significant pathology at all periods of observation with the peak of their manifestation on the 7th day. In glial cells and axons of nerve fibers from the 1st day of the study, signs of compensatory and restorative processes were found: they increased protein-synthesizing and energy-forming functions that were aimed at restoring the damaged ultrastructure. It is established, that 3 hours after the injection of a mixture of alcohols, reactive changes in the structures of the optic nerve of rats took place, which from the 1st day develop into pathological changes and are observed up to 14 days with the peak of their activity on the 7th day of the study. After the use of methanol 100%, the ultrastructure of the optic nerve of rats is more damaged than after the injection of a mixture of alcohols. It is proved, that methanol has a leading place in the development of pathological changes in structures of the optic nerve after the injection of a mixture of alcohols.

Axons are complex subcellular compartments that are extremely long in relation to cell bodies, especially in peripheral nerves. Many processes are required and regulated during axon injury, including anterograde and retrograde transport, glia-to-axon macromolecular transfer, and local axonal protein synthesis. Many in vitro omics approaches have been used to gain insight into these processes, but few have been applied in vivo. Here we adapted the osmotic ex vivo axoplasm isolation method and analyzed the adult rat sciatic-nerve-extruded axoplasm by label-free quantitative proteomics before and after injury. 2087 proteins groups were detected in the axoplasm, revealing translation machinery and microtubule-associated proteins as the most overrepresented biological processes. Ribosomal proteins (73) were detected in the uninjured axoplasm and increased their levels after injury but not within whole sciatic nerves. Meta-analysis showed that detected ribosomal proteins were present in in vitro axonal proteomes. Because local protein synthesis is important for protein localization, we were interested in detecting the most abundant newly synthesized axonal proteins in vivo. With an MS/MS-BONCAT approach, we detected 42 newly synthesized protein groups. Overall, our work indicates that proteomics profiling is useful for local axonal interrogation and suggests that ribosomal proteins may play an important role, especially during injury.

As one of the most exonerative, competitive, and abundant nanoparticles in curative uses, silver nanoparticles (AgNPs) play a growing important role in developing global neurodegeneration. Herein, we inspected the neurotoxic and histopathological effects of the oral dose of 26.9 nm citrate-coated AgNPs (100 and 1000 mg/kgbw, 28 days) on the brain conductivity and permittivity combined with neurotransmitter assays. While male mice in the control group were given deionized water. In terms of biophysical levels, the brain electric conductivity and relative permittivity were significantly decreased in the 26.9 nm citrate-coated AgNP treated groups versus the controls. Besides, 26.9 nm citrate-coated AgNP treatment resulted in a significant deficiency in the concentrations of brain acetylcholine esterase, dopamine, and serotonin. Total brain contents of silver ion significantly increased in a dose-dependent manner. Further, light and electron microscopy revealed a progressive disruption in the lamellar pattern of the myelinated axons of the nerve fibers, in addition to the accumulation of nanosilver in lysosomes and swollen mitochondria in axoplasm. In conclusion, 26.9 nm citrate-coated AgNPs are capable of gaining access to the brain of mice and causing electric conductivity and relative permittivity damage along with a high degree of cellular toxicity in the brain tissue. Therefore, the present study highlights, for the first time, the adverse effects of the citrate-coated AgNPs to the brain of mice and raises the concern of their probable neurotoxic impacts which is helpful for conclusive interpretation of future behavioral and potential neurodegeneration-based aspects. It would be of interest to investigate citrate-coated AgNPs mediated axonal relevant-signal transduction levels in future studies.

Axoplasmic fluid properties for neuronal excitation have been investigated with respect to temperature. Density, the mass fraction of ions and rate of addition of ions are the parameters considered for characterizing axoplasmic fluid properties. The behavior of these parameters has been analyzed with respect to the changes in temperature ranging from -5 degree Celsius to 35 degree Celsius. The temperature has been defined using Q10of3 coefficient as done in the Hodgkin-Huxley model. The trend of these parameters at different temperatures has been depicted along the axonal length represented through x-axis of the graphs. The conduction velocities of the above said parameters have also been recorded at different temperatures. The range [-5,35] degree Celsius has been increased by 20 degrees, 10 degree on the lower side and 10 degree on the upper side of the range [-5,25] degree Celsius and it is found that temperature dependency using Q10of3 coefficient for said parameters is valid only in the temperature ranging from 5 degree Celsius to 25 degree Celsius as it is for membrane voltage in the Hodgkin-Huxley model. These findings strongly support the obtained results and also suggest obtaining the temperature coefficient value which is applicable for a wider range of temperatures impacting neuronal excitation.

In eukaryotic cells, with the exception of the specialized genomes of mitochondria and plastids, all genetic information is sequestered within the nucleus. This arrangement imposes constraints on how the information can be tailored for different cellular regions, particularly in cells with complex morphologies like neurons. Although messenger RNAs (mRNAs), and the proteins that they encode, can be differentially sorted between cellular regions, the information itself does not change. RNA editing by adenosine deamination can alter the genome’s blueprint by recoding mRNAs; however, this process too is thought to be restricted to the nucleus. In this work, we show that ADAR2 (adenosine deaminase that acts on RNA), an RNA editing enzyme, is expressed outside of the nucleus in squid neurons. Furthermore, purified axoplasm exhibits adenosine-to-inosine activity and can specifically edit adenosines in a known substrate. Finally, a transcriptome-wide analysis of RNA editing reveals that tens of thousands of editing sites (>70% of all sites) are edited more extensively in the squid giant axon than in its cell bodies. These results indicate that within a neuron RNA editing can recode genetic information in a region-specific manner.

Conventional histomorphometry of peripheral nerve entails lengthy chemical processing, ultrathin sectioning in resin, and imaging by light or electron microscopy. Multiphoton microscopy techniques exist enabling label-free and in vivo imaging of histological samples. Third-harmonic-generation microscopy has recently been demonstrated effective for imaging the myelin sheath of peripheral nerve axons in animal models. Herein, we characterize use of second and third harmonic generation microscopy for label-free imaging of murine and human peripheral nerve via a novel multicolor multiphoton microscope based on a single excitation wavelength at 1300 nm. Second harmonic generation signal from collagen centered about 650 nm delineates neural connective tissue, while third harmonic general signal centered about 433 nm delineates myelin and other lipids. In transgenic mice expressing yellow fluorescent protein linked to the thy1 promoter, three-photon-excitation with emission peak at 527 nm delineates axoplasm. We compare label-free multiphoton imaging of murine and human peripheral nerve against conventional chemical stains and discuss clinical implications of this approach in guiding intraoperative decision making in nerve transfer procedures.

The objective of this pioneering study was to assess potentially neuroprotective properties of topiramate (TPM), a broad spectrum and newer-generation antiepileptic used against damage to synaptic endings of the temporal lobe neocortex in experimental hyperthermia-induced seizures (HS). TPM (80 mg/kg b.m.) was administered in young male Wistar rats with an intragastric tube before and immediately after HS. Specimens (1 mm3) collected from the neocortex, fixed via transcardial perfusion with paraformaldehyde and glutaraldehyde solution, were routinely processed for transmission-electron microscopic study, i.e., for descriptive and morphometric analysis. The ultrastructure of neocortical neuropil components affected by hyperthermic stress showed distinct swelling of pre and post-synaptic axodendritic and axospinal endings, including total disintegration. Mitochondria were markedly damaged in synaptic structures. Axoplasm of presynaptic boutons contained a decreased number of synaptic vesicles. Synaptic junctions showed active zone-shortening. Preventive administration of TPM before HS induction demonstrated neuroprotective effects against synaptic damage in approximately 1/4 of these structures. Interestingly, beneficial effects on synapsis morphology were more common in perivascular zones close to well-preserved capillaries. They were demonstrated by smaller swelling of both presynaptic and postsynaptic parts, well-preserved mitochondria, an increased number and regular distribution of synaptic vesicles within axoplasm, and a significantly increased synaptic active zones. However, topiramate used directly after HS was ineffective in the prevention of hyperthermia-evoked synaptic injury. Our findings support the hypothesis that topiramate applied before HS can protect some neocortical synapses via the vascular factor by enhancing blood–brain barrier components and improving the blood supply of gray matter in the temporal lobe, which may be significant in febrile seizure-prevention in children.

To describe clinical features, disease course, treatment response, and sural nerve biopsy findings in a patient with chronic sensory ataxic neuropathy, Binet stage A chronic lymphocytic leukemia, and monoclonal IgMλ paraprotein against ganglioside GD1b. During 9 months of hospitalization at two neurologic centers, the patient underwent serial neurologic examinations, neurophysiologic studies, imaging investigations, extensive laboratory work-up, bone marrow, and sural nerve biopsies. The patient had a severe progressive sensory neuropathy accompanied by motor involvement, dysautonomia, and marked bulbar weakness with preserved ocular movements. Conduction studies were characterized by prolonged F-wave minimal latencies, prolonged distal latencies, reduction of compound motor action potentials, and absence of sensory nerve action potentials. Sural nerve biopsy showed endoneurial edema, axonal degeneration, and regeneration, in the absence of cellular inflammation, macrophagic activation, and B-lymphocyte infiltration; no IgM or complement deposition was detected. Myelinated fibers showed redundant/abnormally thickened myelin, myelin vacuolation, and frank intramyelinic edema with condensed axoplasm. Ultrastructural features included axo-glial detachment, disruption of membrane integrity, and myelin uncompaction. This study shows that monospecific anti-GD1b IgM paraprotein is associated with non-inflammatory nerve damage. We suggest that the loss of myelin and axonal integrity reflects antibody-induced disruption of membrane lipid rafts.

The present study aimed at exploring a potentially neuroprotective effect of topiramate (TPM), one of the most commonly used newer-generation, broad-spectrum, antiepileptic drugs against ultrastructural damage of hippocampal synaptic endings in the experimental model of febrile seizures (FS). The study used male young Wistar rats aged 22-30 days, divided into three experimental groups and the control group. Brain maturity in such animals corresponds to that of 1- or 2-year-old children. Hyperthermic stress was evoked by placing animals in a 45°C water bath for four consecutive days. TPM at a dose of 80 mg/kg b.m. was administered with an intragastric tube before and immediately after FS. Specimens (1 mm3) collected from the hippocampal CA1 and CA3 sectors, fixed via transcardial perfusion with a solution of paraformaldehyde and glutaraldehyde, were routinely processed for transmission-electron microscopic analysis. Advanced ultrastructural changes induced by hyperthermic stress were manifested by distinct swelling of hippocampal pre- and post-synaptic axodendritic and axospinal endings, including their vacuolization and disintegration. The axoplasm of the presynaptic boutons contained a markedly decreased number of synaptic vesicles and their abnormal accumulation in the active synaptic region. The synaptic junctions showed a dilated synaptic cleft and a decreased synaptic active zone. TPM used directly after FS was ineffective in the prevention of hyperthermia-induced injury of synaptic endings in hippocampal CA1 and CA3 sectors. However, "prophylactic" administration of TPM, prior to FS induction, demonstrated a neuroprotective effect against synaptic damage in approximately 25% of the synaptic endings in the hippocampal sectors, more frequently located in perivascular zones. It was manifested by smaller oedema of both presynaptic and postsynaptic parts, containing well-preserved mitochondria, increased number and regular distribution of synaptic vesicles within the axoplasm, and increased synaptic active zone. Our current and previous findings suggest that TPM administered "prophylactically", before FS, could exert a favourable effect on some synapses, indirectly, via the vascular factor, i.e. protecting blood-brain barrier components and through better blood supply of the hippocampal CA1 and CA3 sectors, which may have practical implications.

Background: Zinc oxide nanoparticles (ZnONPs) are one of metal nanoparticles that have widespread use in many fields.Objective: To investigate the effect of ZnONPs on cerebellar cortex of rats through histological and immunohistochemical study.Materials and methods: Thirty adult male albino rats were divided into three groups; group I (control), Group II (ZnONP-1 treated group) which received orally 50 mg/kg of ZnONP for two months and Group III (ZnONP-1I treated group) which received orally 200 mg/kg of ZnONP for two months. Specimens of the cerebellar cortex were processed for histological and immunohistochemical study. Morphometric and statistical analysis were carried out.Results: Group II showed Purkinje cells were crowded in many layers surrounded by perineuronal vacuoles and had pyknotic nuclei. They had cytoplasmic vacuoles and perinuclear Golgi apparatus revealed fragmented dilated cisternae. Nearby Bergmann astrocyte cells had highly vacuolated cytoplasm and the nerve fibers were also affected and showed dysmyleination (disrupted myelin sheath). Immunohistochemical study of the same group showed Purkinje cell cytoplasm had positive immunoreactions for calretinin proteins. In group III, there was a wide spread of neuronal affection to the degree of loss of many of Purkinje cells leaving empty spaces. Ultrastructurly, their cytoplasm appeared with multiple variable sized and had dilated mitochondria with disrupted cristae. The Bergmann astrocytes revealed nuclei with disrupted nuclear envelope and nearly absence their cytoplasmic organelle and there was more affection to the nerve fibers in the form of vacuolated axoplasm and demyelination (areas of myelin loss) beside dysmyleination. Immunohistochemical study of group III showed Purkinje cells cytoplasm with negative immunoreactions for calretinin proteins.Conclusion: Intake of ZnONPs induced various adverse alterations in the histological and immunohistochemical structures of cerebellar cortex indicating the occurrence of neurotoxicity. These changes were exaggerated with increasing the dose of their intake.

In several pathological conditions, such as coronavirus infections, multiple sclerosis, Alzheimer's and Parkinson's diseases, the physiological shape of axons is altered and a periodic sequence of bulges appears. Experimental evidences suggest that such morphological changes are caused by the disruption of the microtubules composing the cytoskeleton of the axon. In this paper, we develop a mathematical model of damaged axons based on the theory of continuum mechanics and nonlinear elasticity. The axon is described as a cylinder composed of an inner passive part, called axoplasm, and an outer active cortex, composed mainly of F-actin and able to contract thanks to myosin-II motors. Through a linear stability analysis we show that, as the shear modulus of the axoplasm diminishes due to the disruption of the cytoskeleton, the active contraction of the cortex makes the cylindrical configuration unstable to axisymmetric perturbations, leading to a beading pattern. Finally, the non-linear evolution of the bifurcated branches is investigated through finite element simulations.

The site of origin of amyotrophic lateral sclerosis (ALS), although unsettled, is increasingly recognized as being cortico-fugal, which is a dying-forward process primarily starting in the corticomotoneuronal system. A variety of iterations of this concept date back to over 150 years. Recently, the hallmark TAR DNA-binding protein 43 (TDP-43) pathology, seen in >95% of patients with ALS, has been shown to be largely restricted to corticofugal projecting neurons (“dying forward”). Possibly, soluble but toxic cytoplasmic TDP-43 could enter the axoplasm of Betz cells, subsequently causing dysregulation of nuclear protein in the lower brainstem and spinal cord anterior horn cells. As the disease progresses, cortical involvement in ALS becomes widespread, including or starting with frontotemporal dementia, implying a broader view of ALS as a brain disease. The onset at the motor and premotor cortices should be considered a nidus at the edge of multiple cortical networks which eventually become disrupted, causing failure of a widespread cortical connectome.

Proteins generated by localized mRNA translation in axons support nerve regeneration through retrograde injury signaling and localized axon growth mechanisms. RNA binding proteins (RBP) are needed for this and other aspects of post-transcriptional control of localized mRNAs, but only a limited number of axonal RBPs have been reported. We used a targeted mass spectrometry approach to profile the axonal RBPs in naïve, injured and regenerating PNS axons. We detected 76 axonal proteins that are reported to have RNA binding activity, with the levels of several of these axonal RBPs changing with axonal injury and regeneration. These axonal RBPs with altered axoplasm levels include KHSRP that we previously reported decreases neurite outgrowth in developing CNS neurons. We show that KHSRP levels rapidly increase in sciatic nerve axons after crush injury and remain elevated increasing in levels out to 28 days post-sciatic nerve crush injury. Khsrp mRNA localizes into axons and the rapid increase in axonal KHSRP after axotomy is mediated by the local translation of its mRNA. KHSRP binds to mRNAs with a 3’UTR AU-rich element and targets those mRNAs to the cytoplasmic exosome for degradation. KHSRP knockout mice show increased axonal levels of defined KHSRP target mRNAs, Gap43 and Snap25 mRNAs, following sciatic nerve injury and accelerated nerve regeneration in vivo. These data indicate that axonal translation of Khsrp mRNA following nerve injury serves to destabilize other axonal mRNAs and slow axon regeneration.

Regeneration after injury occurs in axons that lie in the peripheral nervous system but fails in the central nervous system, thereby limiting functional recovery. Differences in axonal signalling in response to injury that might underpin this differential regenerative ability are poorly characterized. Combining axoplasmic proteomics from peripheral sciatic or central projecting dorsal root ganglion (DRG) axons with cell body RNA-seq, we uncover injury-dependent signalling pathways that are uniquely represented in peripheral versus central projecting sciatic DRG axons. We identify AMPK as a crucial regulator of axonal regenerative signalling that is specifically downregulated in injured peripheral, but not central, axons. We find that AMPK in DRG interacts with the 26S proteasome and its CaMKIIα-dependent regulatory subunit PSMC5 to promote AMPKα proteasomal degradation following sciatic axotomy. Conditional deletion of AMPKα1 promotes multiple regenerative signalling pathways after central axonal injury and stimulates robust axonal growth across the spinal cord injury site, suggesting inhibition of AMPK as a therapeutic strategy to enhance regeneration following spinal cord injury.

Axonal protein synthesis has been shown to play a role in developmental and regenerative growth, as well as in the maintenance of the axoplasm in a steady state. Recent studies have begun to identify the mRNAs localized in axons, which could be translated locally under different conditions. Despite that by now hundreds or thousands of mRNAs have been shown to be localized into the axonal compartment of cultured neurons in vitro, knowledge of which mRNAs are localized in mature myelinated axons is quite limited. With the purpose of characterizing the transcriptome of mature myelinated motor axons of peripheral nervous systems, we modified the axon microdissection method devised by Koenig, enabling the isolation of the axoplasm RNA to perform RNA-seq analysis. The transcriptome analysis indicates that the number of RNAs detected in mature axons is lower in comparison with in vitro data, depleted of glial markers, and enriched in neuronal markers. The mature myelinated axons are enriched for mRNAs related to cytoskeleton, translation, and oxidative phosphorylation. Moreover, it was possible to define core genes present in axons when comparing our data with transcriptomic data of axons grown in different conditions. This work provides evidence that axon microdissection is a valuable method to obtain genome-wide data from mature and myelinated axons of the peripheral nervous system, and could be especially useful for the study of axonal involvement in neurodegenerative pathologies of motor neurons such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophies (SMA).

The existence of different conductive patterns in unmyelinated and myelinated axons is uncertain. It seems that considering exclusively physical electrical phenomena may be an oversimplification. A novel interpretation of the mechanism of nerve conduction in myelinated nerves is proposed, to explain how the basic mechanism of nerve conduction has been adapted to myelinated conditions. The neurilemma would bear the voltage-gated channels and Na+/K+-ATPase in both unmyelinated and myelinated conditions, the only difference being the sheath wrapping it. The dramatic increase in conduction speed of the myelinated axons would essentially depend on an increment in ATP availability within the internode: myelin would be an aerobic ATP supplier to the axoplasm, through connexons. In fact, neurons rely on aerobic metabolism and on trophic support from oligodendrocytes, that do not normally duplicate after infancy in humans. Such comprehensive framework of nerve impulse propagation in axons may shed new light on the pathophysiology of nervous system disease in humans, seemingly strictly dependent on the viability of the pre-existing oligodendrocyte.

Experiments have demonstrated that signals in nerve fibers are composed by electrical and mechanical components. In this paper a coupled mathematical model is described which unites the governing equations for the action potential, the pressure wave in the axoplasm and the longitudinal and the transverse waves in the surrounding biomembrane into one system of equations. As a solution of this system, an ensemble of waves is generated. The main hypotheses of such a model are related to the nature of coupling forces between the single waves in the ensemble. These coupling forces are assumed to have bi-polar shapes leading to energetically stable solutions. The in silico modeling demonstrates the qualitative resemblance of computed wave profiles to experimental ones. The ideas of possible experimental validation of the model are briefly described.

Local translation of membrane proteins in neuronal subcellular domains like soma, dendrites and axon termini is well-documented. In this study, we isolated the electrical signaling unit of an axon by dissecting giant axons from mature squids (Dosidicus gigas). Axoplasm extracted from these axons was found to contain ribosomal RNAs, ~8000 messenger RNA species, many encoding the translation machinery, membrane proteins, translocon and signal recognition particle (SRP) subunits, endomembrane-associated proteins, and unprecedented proportions of SRP RNA (~68% identical to human homolog). While these components support endoplasmic reticulum-dependent protein synthesis, functional assessment of a newly synthesized membrane protein in axolemma of an isolated axon is technically challenging. Ion channels are ideal proteins for this purpose because their functional dynamics can be directly evaluated by applying voltage clamp across the axon membrane. We delivered in vitro transcribed RNA encoding native or Drosophila voltage-activated Shaker KV channel into excised squid giant axons. We found that total K+ currents increased in both cases; with added inactivation kinetics on those axons injected with RNA encoding the Shaker channel. These results provide unambiguous evidence that isolated axons can exhibit de novo synthesis, assembly and membrane incorporation of fully functional oligomeric membrane proteins.

The ramus communicans, neural connection between medial and lateral plantar nerves of the horse, was transected to determine the degree to which medial and lateral plantar nerves contribute to the plantar ramus. After 2 months, sections of plantar nerves immediately proximal and distal to the communicating branch were collected and processed for electron microscopy. All examined nerves had undergone Wallerian degeneration and contained regenerating and mature fibers. Layers of the myelin sheath were separated by spaces and vacuoles, indicating demyelination of medial and lateral plantar nerves. Shrunken axons varied in diameter and were surrounded by an irregular axolemma. Shrunken axoplasm of both myelinated and non-myelinated fibers contained ruptured mitochondria and cristae, disintegrating cytoskeleton, and vacuoles of various sizes. The cytoplasm of neurolemmocytes contained various-sized vesicles, ruptured mitochondria within a fragile basal lamina and myelin whorls of multilayered structures indicative of Wallerian degeneration. These ultrastructural changes, found proximal and distal to the ramus in medial and lateral plantar nerves, suggest that axonal flow is bi-directional through the ramus communicans of the pelvic limbs of horses, a previously unreported finding. As well, maturity of nerves proximal and distal to the ramus indicates that all nerve fibers do not pass through the ramus.

Pseudapocryptes lanceolatus (Bloch and Schneider) is a monomorphic protogynous hermaphrodite teleost that possesses ovotestis as gonadal unit of reproductive structure. At the onset of breeding season (i.e., June-July), the ovarian tissue is gradually differentiating into female-phased P. lanceolatus. At the same time, the pear-shaped crypt cells (a type of neuron) are frequently appeared at apical part of pseudostratified olfactory neuroepithelium of P. lanceolatus. The crypt neuron is characterized by the presence of sunken cilia and microvilli at the proximal region. The features of subcellular organelles are also explored in lieu of their probable functional significance. The nucleoplasm of mature crypt neuron shows chromatin granules having diameter: 15-25 nm. This cell undergoes neural apoptosis at the end of breeding phase (i.e., October-November). Fragmented chromatin fibers with numerous chromatin granules (diameter: 25-30 nm) in nucleoplasm and lysosomal diversity are the most notable characters of apoptotic crypt neuron. The large accumulation of heterochromatin chromatins in nucleoplasm is also marked under fluorescence microscope. The frequent presence of acetylcholinesterase-positive vesicles in axoplasm of crypt neurons is also a prime subcellular indicator for inhibition of neural transmission of olfactory signals. Therefore, it is concluded that the sex differentiation in P. lanceolatus and occurrence of crypt neuron in olfactory neuroepithelium are interrelated events during the reproductive period. Consequently, we hypothesized that the crypt neuron plays an active role in the implementation of unique reproductive strategy through recognition of pheromonal cues within the social organization of P. lanceolatus.

The epidemiological, clinic and morphological (pathological and ultrastructural) aspects of four outbreaks of copper deficiency affecting 21- to 90-day-old pigs in the Northeast region of Brazil are reported. Clinical signs began with paraparesis and ataxia and progressed to flaccid or spastic paralysis of the pelvic and thoracic limbs, followed by sternal and/or lateral recumbence. In addition, some animals showed dog-sitting position and intention tremors. The clinical manifestation period was 5-20 days. Significant gross lesions were not observed; however, microscopically, symmetrical degeneration of the white matter with ballooned myelin sheaths containing occasional macrophages was observed, mainly in the spinal cord. Two pigs presented with necrosis ad loss of Purkinje cells and ectopic Purkinje cells in the granular layer and cerebellar white matter. A ultrastructural analysis showed different degrees of damage of myelinated axons in the spinal segments, including an absence of the axoplasm structures with only axonal residues remaining. The myelin sheaths were degenerated and often collapsed into the space previously occupied by the axon. These results suggest that myelin degeneration is secondary to the axonal lesion. Finally, the concentration of copper in the liver was determined using atomic absorption spectrophotometry and was found to be low (ranging from 2.2 to 10.8 ppm). In conclusion, in the Brazilian semiarid region, Cu deficiency occurs in 21 to 90-day-old pigs that ingested different types of waste in their food. RESUMO: São relatados os achados epidemiológicos, clínicos e morfológicos (patológicos e ultraestruturais) de quatro surtos de deficiência de cobre em suínos afetados entre 21 e 90 dias de idade na região Nordeste do Brasil. Os sinais clínicos iniciaram com paraparesia e ataxia, que progrediu a paralisia flácida ou espástica dos membros pélvicos e torácicos, seguido de decúbito esternal e/ou lateral. Além disso, alguns animais apresentaram posição de cão sentado e tremores de intenção. O período de manifestação clínica variou de 5-20 dias. Não foram observadas lesões macroscópicas significativas; no entanto, microscopicamente, foi observada degeneração simétrica da substância branca com fragmentação das bainhas de mielina, contendo ocasionais macrófagos, principalmente na medula espinal. Dois suínos apresentaram necrose e perda de células de Purkinje e células de Purkinje ectópicos na camada granular da substância branca cerebelar. A análise ultraestrutural mostrou diferentes graus de lesões em axônios mielinizados em segmentos da medula espinhal, incluindo o desaparecimento de estruturas do axoplasma, restando apenas restos axonais. A bainha de mielina encontrava-se degenerada e muitas vezes, colapsada dentro do espaço previamente ocupado pelo axônio. Esses resultados sugerem que a degeneração da mielina é secundária à lesão axonal. Finalmente, a concentração do cobre no fígado foi determinada usando espectrometria de absorção atômica e revelou baixos valores (variando de 2,2-10,8ppm). Conclui-se que na região semiárida do Brasil ocorre deficiência de cobre em suínos de 21 a 90 dias de idade alimentados com diferentes tipos de resíduos.

Rett syndrome (RTT) is a neurological disorder characterized by motor and cognitive impairment, autonomic dysfunction and a loss of purposeful hand skills. In the majority of cases, typical RTT is caused by de novo mutations in the X-linked gene, MECP2. Alterations in the structure and function of neurons within the central nervous system of RTT patients and Mecp2-null mouse models are well established. In contrast, few studies have investigated the effects of MeCP2-deficiency on peripheral nerves. In this study, we conducted detailed morphometric as well as functional analysis of the sciatic nerves of symptomatic adult female Mecp2+/- mice. We observed a significant reduction in the mean diameter of myelinated nerve fibers in Mecp2+/- mice. In myelinated fibers, mitochondrial densities per unit area of axoplasm were significantly altered in Mecp2+/- mice. However, conduction properties of the sciatic nerve of Mecp2 knockout mice were not different from control. These subtle changes in myelinated peripheral nerve fibers in heterozygous Mecp2 knockout mice could potentially explain some RTT phenotypes.

The pathological process underlying sporadic amyotrophic lateral sclerosis (sALS) that is associated with the formation of cytoplasmic inclusions of a nuclear protein (TDP-43) is confined to only a few types of long-axoned projection neurons. The giant Betz pyramidal cells of the primary motor neocortex as well as large α-motor neurons of the lower brainstem and spinal cord become involved early. In the human brain, these 2 neuronal types are to a large extent interconnected by monosynaptic axonal projections. The cell nuclei of affected neurons gradually forfeit their normal expression of the protein TDP-43. In α-motor neurons, this nuclear loss is followed by the formation of insoluble TDP-43-immunopositive inclusions in the cytoplasm, whereas in Betz cells the loss of nuclear expression remains for an unknown period of time unaccompanied by somatodendritic and/or axoplasmic aggregations. It is possible that in cortical pyramidal cells (Betz cells) the nuclear clearing initially leads to the formation of an abnormal but still soluble cytoplasmic TDP-43 which may enter the axoplasm and, following transmission via direct synaptic contacts, induces anew TDP-43 dysregulation and aggregation in recipient neurons. The trajectory of the spreading pattern that consecutively develops during the course of sALS is consistent with the dissemination from chiefly cortical projection neurons via axonal transport through direct synaptic contacts leading to the secondary induction of TDP-43-containing inclusions within recipient nerve cells in involved subcortical regions.

Objective: This study explored the effect of circadian disorder on structure and function of neurons in hippocampus of mice. Methods: Forty male ICR mice were randomly divided into rhythm disorder group (RDG) and normal rhythm group (NRG). The RDG was treated with 3 h light/5 h dark and 5 h light/3 h dark light–dark (LD) cycle alternately. The normal rhythm group was treated with 12/12 h LD cycle. Electron microscope was used to detect the mouse hippocampal cell ultrastructure. Morris water maze was used to test mice cognitive function. The brain slice electric physiological techniques were used to detect synapses in the hippocampal Long-term potentiation (LTP) effect. Results: The time of through central area of RDG was less than that of NRG. The axoplasm in anterior-posterior membranes of synapses of RDG was dissolved and synaptic vesicles of RDG were decreased. Conclusion: Circadian rhythm disorder induced by irregular light–dark circle can lead to the structural damage of hippocampal neurons a...

The cornea is the most highly innervated tissue in the body. It is generally accepted that corneal stromal nerves penetrate the epithelial basal lamina giving rise to intra-epithelial nerves. During the course of a study wherein we imaged corneal nerves in mice, we observed a novel neuronal-epithelial cell interaction whereby nerves approaching the epithelium in the cornea fused with basal epithelial cells, such that their plasma membranes were continuous and the neuronal axoplasm freely abutted the epithelial cytoplasm. In this study we sought to determine the frequency, distribution, and morphological profile of neuronal-epithelial cell fusion events within the cornea. Serial electron microscopy images were obtained from the anterior stroma in the paralimbus and central cornea of 8-10 week old C57BL/6J mice. We found evidence of a novel alternative behavior involving a neuronal-epithelial interaction whereby 42.8% of central corneal nerve bundles approaching the epithelium contain axons that fuse with basal epithelial cells. The average surface-to-volume ratio of a penetrating nerve was 3.32, while the average fusing nerve was smaller at 1.39 (p ≤ 0.0001). Despite this, both neuronal-epithelial cell interactions involve similarly sized discontinuities in the basal lamina. In order to verify the plasma membrane continuity between fused neurons and epithelial cells we used the lipophilic membrane tracer DiI. The majority of corneal nerves were labeled with DiI after application to the trigeminal ganglion and, consistent with our ultrastructural observations, fusion sites recognized as DiI-labeled basal epithelial cells were located at points of stromal nerve termination. These studies provide evidence that neuronal-epithelial cell fusion is a cell-cell interaction that occurs primarily in the central cornea, and fusing nerve bundles are morphologically distinct from penetrating nerve bundles. This is, to our knowledge, the first description of neuronal-epithelial cell fusion in the literature adding a new level of complexity to the current understanding of corneal innervation.

Recent studies have revealed the complex structure of nerve signals in axons. There is experimental evidence that the propagation of an electrical signal (action potential) is accompanied by mechanical and thermal effects. In this paper, first an overview is presented on experimental results and possible mechanisms of electromechanophysiological couplings which govern the signal formation in axons. This forms a basis for building up a mathematical model describing an ensemble of waves. Three physical mechanisms responsible for coupling are (i) electric-lipid bi-layer interaction resulting in the mechanical wave in biomembrane; (ii) electric-fluid interaction resulting in the mechanical wave in the axoplasm; (iii) electric-fluid interaction resulting in the temperature change in axoplasm. The influence of possible changes in variables which could have a role for interactions are analysed and the concept of internal variables introduced for describing the endothermic processes. The previously proposed mathematical model is modified reflecting the possible physical explanation of these interactions., Submission updated to correct few typos and to remove one reference being present twice

Polyethylene glycol repair (PEG-fusion) of severed sciatic axons restores their axoplasmic and membrane continuity, prevents Wallerian degeneration, maintains muscle fiber innervation, and greatly improves recovery of voluntary behaviors. We examined alterations in spinal connectivity and motoneuron dendritic morphology as one potential mechanism for improved behavioral function after PEG-fusion. At 2–112 days after a single-cut or allograft PEG-fusion repair of transected or ablated sciatic nerves, the number, size, location, and morphology of motoneurons projecting to the tibialis anterior muscle were assessed by retrograde labeling. For both lesion types, labeled motoneurons were found in the appropriate original spinal segment, but also in inappropriate segments, indicating mis-pairings of proximal-distal segments of PEG-fused motor axons. Although the number and somal size of motoneurons was unaffected, dendritic distributions were altered, indicating that PEG-fusion preserves spinal motoneurons but reorganizes their connectivity. This spinal reorganization may contribute to the remarkable behavioral recovery seen after PEG-fusion repair.

The main limitation on axon regeneration in the peripheral nervous system (PNS) is the slow rate of regrowth. We recently demonstrated that nerve regeneration can be accelerated by axonal G3BP1 aggregate disassembly, releasing axonal mRNAs for local translation to support growth. Here we show that G3BP1 phosphorylation by Casein Kinase 2α (CK2α) regulatesdisassembly of mRNA storage structures in injured sensory neurons. Axonal CK2α activity is temporally and spatially restricted by mTOR and calcium dependent local translation of Csnk2a1 mRNA in axons after injury. CK2α appearance in axons after PNS nerve injury correlates with disassembly of axonal stress granule-like aggregates and increased axon growth. Changes in axoplasmic calcium enableaxonal translation to switch from early synthesis of proteins needed for retrograde injury signaling to later synthesis of growth-promoting proteins from mRNA pools released by CK2α regulation of G3BP1. Hence, calcium-dependent G3BP1 phosphorylation regulates neuronal regeneration.

The physical structure of neurons - dendrites converging on the soma, with an axon conveying activity to distant locations - is uniquely tied to their function. To perform their role, axons need to maintain structural precision in the soft, gelatinous environment of the central nervous system and the dynamic, flexible paths of nerves in the periphery. This requires close mechanical coupling between axons and the surrounding tissue, as well as an elastic, robust axoplasm resistant to pinching and flattening, and capable of sustaining transport despite physical distortion. These mechanical properties arise primarily from the properties of the internal cytoskeleton, coupled to the axonal membrane and the extracellular matrix. In particular, the two large constituents of the internal cytoskeleton, microtubules and neurofilaments, are braced against each other and flexibly interlinked by specialised proteins. Recent evidence suggests that the primary function of neurofilament sidearms is to structure the axoplasm into a linearly organised, elastic gel. This provides support and structure to the contents of axons in peripheral nerves subject to bending, protecting the relatively brittle microtubule bundles and maintaining them as transport conduits. Furthermore, a substantial proportion of axons are myelinated, and this thick jacket of membrane wrappings alters the form, function and internal composition of the axons to which it is applied. Together these structures determine the physical properties and integrity of neural tissue, both under conditions of normal movement, and in response to physical trauma. The effects of traumatic injury are directly dependent on the physical properties of neural tissue, especially axons, and because of axons' extreme structural specialisation, post-traumatic effects are usually characterised by particular modes of axonal damage. The physical realities of axons in neural tissue are integral to both normal function and their response to injury, and require specific consideration in evaluating research models of neurotrauma.

The structural homeostasis is challenging for neurons, whose axons extend up to meters in large animals, and the axoplasmic mass reaches over a thousand times that of the cell body. Thus, the protein demand may overcome the capacity of the cell body to supply the right protein species, to the right place, in the right time. In this context, a body of evidence indicates that glial cells support the axonal maintenance and regenerative responses by diverse mechanisms of intercellular communication. We showed recently that Schwann cells (SC) transfer ribosomes to axons and also enhance regeneration by means of extracellular vesicles known as exosomes that contain mRNAs, miRNAs and proteins. These findings strongly suggest that the nucleus of the SC supports the machinery for protein synthesis of the axon and participates in the specification of the phenotype of the underlying axon. That the genetic programs of many nuclei modulate the axoplasm on a local basis is akin to a syncytium but at variance with it, the nuclei belong to satellite cells. We propose that the SC-axon unit is a functional syncytium. This intercellular organization opens a novel understanding of the nervous system and a new avenue of research into its physiology and disorders © 2016 Wiley Periodicals, Inc.

Polyribosomes, mRNA, and other elements of translational machinery have been reported in peripheral nerves and in elongating injured axons of sensory neurons in vitro, primarily in growth cones. Evidence for involvement of local protein synthesis in regenerating central nervous system (CNS) axons is less extensive. We monitored regeneration of back-labeled lamprey spinal axons after spinal cord transection and detected mRNA in axon tips by in situ hybridization and microaspiration of their axoplasm. Poly(A)+mRNA was present in the axon tips, and was more abundant in actively regenerating tips than in static or retracting ones. Target-specific polymerase chain reaction (PCR) and in situ hybridization revealed plentiful mRNA for the low molecular neurofilament subunit and β-tubulin, but very little for β-actin, consistent with the morphology of their tips, which lack filopodia and lamellipodia. Electron microscopy showed ribosomes/polyribosomes in the distal parts of axon tips and in association with vesicle-like membranes, primarily in the tip. In one instance, there were structures with the appearance of rough endoplasmic reticulum. Immunohistochemistry showed patches of ribosomal protein S6 positivity in a similar distribution. The results suggest that local protein synthesis might be involved in the mechanism of axon regeneration in the lamprey spinal cord. J. Comp. Neurol. 524:3614-3640, 2016. © 2016 Wiley Periodicals, Inc.

In the present study, for the first time, a thermodynamically consistent large deformation theory is developed to model the multi physics problem of axonal swelling which is the hallmark of most of the brain diseases. To this end, first, relevant axonal compartments are explained and then the corresponding model parts are introduced. Next, the problem is formulated as an open thermodynamic system and the consequent constitutive and evolution equations are extracted utilizing the balance laws. Here, a multiplicative decomposition of the deformation gradient is used to capture the active behavior of the axonal actin cortex. After that, specific free energy functions are given for the model parts to complete the framework. Finally, while the developed model is general and can be extended to cover other types of axonal swellings, for the sake of briefness, two swelling modes are explored in the present study: swelling due to hypo-osmotic shocks and volume expansions because of actomyosin disruptions. To this end, three relevant sets of experimental data available in the literature are chosen to be investigated; free equilibrium swelling of squid axoplasm, transient swelling of PC12 neurites due to hypo-osmotic shocks and steady state as well as transient swellings of embryonic Drosophila axons due to blocking myosin motors. Comparative study between model predictions with realistic estimated parameters and the corresponding experimental data demonstrates that the model can successfully predict both axonal swellings. The key findings of this study are as follows: first, it is shown that the kinetics of axonal swelling is surface limited and hence there is no need to consider the details of water diffusion inside the axoplasm. In fact, the axoplasm swelling can be considered instantaneous in the presence of the axolemma barrier. Second, axonal swelling happens mainly in its radial direction due to its structural and geometrical constraints. Third, the multiphasic nature of the axoplasm can be accurately modeled as an ideal polyelectrolyte hydrogel and finally the active contractile forces can be ignored for volume expansions due to hypo-osmotic shocks as the osmotic pressures are much bigger than the corresponding stresses due to active deformations.

The main limitation on axon regeneration in the peripheral nervous system (PNS) is the slow rate of regrowth. We recently reported that nerve regeneration can be accelerated by axonal G3BP1 granule disassembly, releasing axonal mRNAs for local translation to support axon growth. Here, we show that G3BP1 phosphorylation by casein kinase 2α (CK2α) triggers G3BP1 granule disassembly in injured axons. CK2α activity is temporally and spatially regulated by local translation of Csnk2a1 mRNA in axons after injury, but this requires local translation of mTor mRNA and buffering of the elevated axonal Ca2+ that occurs after axotomy. CK2α's appearance in axons after PNS nerve injury correlates with disassembly of axonal G3BP1 granules as well as increased phospho-G3BP1 and axon growth, although depletion of Csnk2a1 mRNA from PNS axons decreases regeneration and increases G3BP1 granules. Phosphomimetic G3BP1 shows remarkably decreased RNA binding in dorsal root ganglion (DRG) neurons compared with wild-type and non-phosphorylatable G3BP1; combined with other studies, this suggests that CK2α-dependent G3BP1 phosphorylation on Ser 149 after axotomy releases axonal mRNAs for translation. Translation of axonal mRNAs encoding some injury-associated proteins is known to be increased with Ca2+ elevations, and using a dual fluorescence recovery after photobleaching (FRAP) reporter assay for axonal translation, we see that translational specificity switches from injury-associated protein mRNA translation to CK2α translation with endoplasmic reticulum (ER) Ca2+ release versus cytoplasmic Ca2+ chelation. Our results point to axoplasmic Ca2+ concentrations as a determinant for the temporal specificity of sequential translational activation of different axonal mRNAs as severed axons transition from injury to regenerative growth.

In this paper, spatio-temporal characterization of axoplasmic fluid pressure has been performed with respect to ionic diffusivities. It has been observed that the propagation speed of axoplasmic fluid pressure is 19.5 m/s when longitudinal ionic diffusivities are considered along with ionic conductances at a temperature of \(18.5\,^\circ \text {C}\). However, this propagation speed of axoplasmic fluid pressure increases to 19.7 m/s when longitudinal ionic diffusivities are considered along with temperature-dependent diffusivities across the membrane at the same temperature of \(18.5\,^\circ \text {C}\). This is an important result where it has been possible to obtain axoplasmic pressure propagation velocities with respect to temperature-dependent ionic diffusivities. Also, based on the fact that increased intracellular pressure may lead to a number of neuronal disorders, temperature-dependent ionic diffusivities can be further fine-tuned to reduce the intracellular pressure and hence avoiding neuronal disorders.

Saltatory conduction is an essential phenomenon to facilitate the fast conduction in myelinated nerves. The conventional conductive models assumed electric circuits with local current along the axonal membrane to explain the nerve conduction in unmyelinated nerves. However, whether such models with local current can be also applied to the saltatory conduction in myelinated nerves is unknown. In this report, I propose a new model of saltatory conduction by focusing on the behavior of electric charges in the axoplasm, not limited to the membrane. In myelinated nerves, because of the large internodal length and the low ion channel density in the internodal segment, the whole cross-section of the internodal axoplasm would contribute to the signal conduction. Because the conducted signals originate from the sodium ion influx through the voltage-gated sodium (NaV) channel at the Ranvier's nodes, an individual conducted signal can be described as a single electrostatic compressional wave of positive charges in the internodal axoplasm. Based on this model, the total number of NaV channels in one Ranvier's node would regulate the strength of the wave. Also, the internodal length would be important for the faster conduction in larger myelinated axons. Based on the linear relationships between axonal diameter, internodal length, and conduction velocity, the internodal length would be inversely proportional to the ratio of the transmitted overall wave strength at a Ranvier's node to the original strength at the proximal adjacent node. This new mathematical model may have wide applicability and usability for the conduction in myelinated nerves.

This chapter discusses experimental and theoretical considerations related to intracellular gradients of calcium and hydrogen ions. The diffusion of calcium ions in cytoplasm cannot be expected to resemble that in free solution. In cytoplasm, a host of Ca-binding and sequestering entities are present, complicating the diffusion process. Calcium gradients from the surface membrane into the axoplasm have been deduced from experiments in which aequorin was injected into the squid giant axon. This protein, extracted from the jelly fish emits light in the presence of calcium. In many types of cells, a rapid transient rise in intracellular calcium has been shown to be a necessary link between an extracellular signal or an electrical event in the surface membrane and some functional activity of the cell. The cell may be considered as a surface membrane dividing an extracellular medium from an intracellular compartment of uniform composition.

KEY POINTS In peripheral myelinated axons of mammalian spinal motor neurons, Ca(2+) influx was thought to occur only in pathological conditions such as ischaemia. Using Ca(2+) imaging in mouse large motor axons, we find that physiological stimulation with trains of action potentials transiently elevates axoplasmic [C(2+)] around nodes of Ranvier. These stimulation-induced [Ca(2+)] elevations require Ca(2+) influx, and are partially reduced by blocking T-type Ca(2+) channels (e.g. mibefradil) and by blocking the Na(+)/Ca(2+) exchanger (NCX), suggesting an important contribution of Ca(2+) influx via reverse-mode NCX activity. Acute disruption of paranodal myelin dramatically increases stimulation-induced [Ca(2+)] elevations around nodes by allowing activation of sub-myelin L-type (nimodipine-sensitive) Ca(2+) channels. The Ca(2+) that enters myelinated motor axons during normal activity is likely to contribute to several signalling pathways; the larger Ca(2+) influx that occurs following demyelination may contribute to the axonal degeneration that occurs in peripheral demyelinating diseases. Activity-dependent Ca(2+) signalling is well established for somata and terminals of mammalian spinal motor neurons, but not for their axons. Imaging of an intra-axonally injected fluorescent [Ca(2+)] indicator revealed that during repetitive action potential stimulation, [Ca(2+)] elevations localized to nodal regions occurred in mouse motor axons from ventral roots, phrenic nerve and intramuscular branches. These [Ca(2+)] elevations (∼ 0.1 μm with stimulation at 50 Hz, 10 s) were blocked by removal of Ca(2+) from the extracellular solution. Effects of pharmacological blockers indicated contributions from both T-type Ca(2+) channels and reverse mode Na(+)/Ca(2+) exchange (NCX). Acute disruption of paranodal myelin (by stretch or lysophosphatidylcholine) increased the stimulation-induced [Ca(2+)] elevations, which now included a prominent contribution from L-type Ca(2+) channels. These results suggest that the peri-nodal axolemma of motor axons includes multiple pathways for stimulation-induced Ca(2+) influx, some active in normally-myelinated axons (T-type channels, NCX), others active only when exposed by myelin disruption (L-type channels). The modest axoplasmic peri-nodal [Ca(2+)] elevations measured in intact motor axons might mediate local responses to axonal activation. The larger [Ca(2+) ] elevations measured after myelin disruption might, over time, contribute to the axonal degeneration observed in peripheral demyelinating neuropathies.

Recently, we have demonstrated that myelin conducts an extramitochondrial oxidative phosphorylation, hypothesizing a novel supportive role for myelin in favor of the axon. We have also hypothesized that the ATP produced in myelin could be transferred thought gap junctions. In this work, by biochemical, immunohistochemical, and electrophysiological techniques, the existence of a connection among myelin to the axon was evaluated, to understand how ATP could be transferred from sheath to the axoplasm. Data confirm a functional expression of oxidative phosphorylation in isolated myelin. Moreover, WB and immunohistochemistry on optic nerve slices show that connexins 32 and 43 are present in myelin and colocalize with myelin basic protein. Interestingly, addition of carbenoxolone or oleamide, two gap junction blockers, causes a decrease in oxidative metabolism in purified myelin, but not in mitochondria. Similar effects were observed on conduction speed in hippocampal Schaffer collateral, in the presence of oleamide. Confocal analysis of optic nerve slices showed that lucifer yellow (that only passes through aqueous pores) signal was found in both the sheath layers and the axoplasma. In the presence of oleamide, but not with oleic acid, signal significantly decreased in the sheath and was lost inside the axon. This suggests the existence of a link among myelin and axons. These results, while supporting the idea that ATP aerobically synthesized in myelin sheath could be transferred to the axoplasm through gap junctions, shed new light on the function of the sheath.

Intrinsic mechanisms that guide damaged axons to regenerate following spinal cord injury remain poorly understood. Manipulation of posttranslational modifications of key proteins in mature neurons could reinvigorate growth machinery after injury. One such modification is acetylation, a reversible process controlled by two enzyme families, the histone deacetylases (HDACs) and the histone acetyl transferases (HATs), acting in opposition. Whereas acetylated histones in the nucleus are associated with upregulation of growth-promoting genes, deacetylated tubulin in the axoplasm is associated with more labile microtubules, conducive to axon growth. This study investigates the effects of HAT and HDAC inhibitors on cultured adult dorsal root ganglia (DRG) neurons and shows that inhibition of HATs by anacardic acid or CPTH2 improves axon outgrowth, whereas inhibition of HDACs by TSA or tubacin inhibits axon growth. Anacardic acid increased the number of axons able to cross an inhibitory chondroitin sulfate proteoglycan border. Histone acetylation but not tubulin acetylation level was affected by HAT inhibitors, whereas tubulin acetylation levels were increased in the presence of the HDAC inhibitor tubacin. Although the microtubule-stabilizing drug taxol did not have an effect on the lengths of DRG axons, nocodazole decreased axon lengths. Determining the mechanistic basis will require future studies, but this study shows that inhibitors of HAT can augment axon growth in adult DRG neurons, with the potential of aiding axon growth over inhibitory substrates produced by the glial scar.