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The present article aims to review state-of-the-art evidence of altered neurobiology and neuroanatomy underlyingpsychiatric symptoms in parkinsonism. This issue covers a wide range of symptoms encompassing anxiety, mooddisorders, psychosis as well as substance abuse and specific compulsive behaviors. Such a complex nosographymakes it impossible to deal with the neurobiology and neuroanatomy of each psychopathological condition perse, unless offering a trivial list of symptoms joined with brief explanations reporting potential causal mechanisms.This approach would only provide a rough synthesis of what previously reported without adding neither novelconcepts nor evidence to improve our insight into the neurobiology of parkinsonism as a psychiatric condition.Therefore, the analytical description of each psychiatric symptom associated with parkinsonism will be avoided butit will be referenced instead. In contrast, the present article will focus on the mechanisms why such a class of nonmotorsymptoms clusters in parkinsonian patients. In addition, we will seek to establish the relationship betweenthe occurrence of a given psychiatric condition and specific parkinsonian phenotypes. Again, an emphasis will begiven to the occurrence of behavioral fluctuations in parkinsonism where both motor and psychiatric symptomsmay possess a specific timing. The timing of these fluctuations will be related to the timing of dopamine substitutiontherapy and involvement of multiple neurotransmitters and brain regions as well. We provide evidence showingthat specific parkinsonian phenotypes (and genotypes) possess a widespread neuropathology, which in turn associatesto a fairly specific psychopathology. In contrast, other phenotypes (and genotypes) bring to very selectiveneuronal degeneration where the occurrence of psychiatric symptoms is rare if not absent at all. These clinicalpathological phenotypes associate with specific molecular mechanisms in the dynamics of neurobiology of disease.

Spinal muscular atrophy (SMA) is a neurogenetic autosomal recessive disorder characterized by degeneration of lower motor neurons. The validation of appropriate animal models is key in fostering SMA research. Recent studies set up an animal model showing long survival and slow disease progression. This model is knocked out for mouse SMN (Smn(-/-)) gene and carries a human mutation of the SMN1 gene (SMN1A2G), along with human SMN2 gene. In the present study we used this knock out double transgenic mouse model (SMN2(+/+); Smn(-/-); SMN1A2G(+/-)) to characterize the spinal cord pathology along with motor deficit at prolonged survival times. In particular, motor neuron loss was established stereologically (44.77%) after motor deficit reached a steady state. At this stage, spared motor neurons showed significant cell body enlargement. Moreover, similar to what was described in patients affected by SMA we found neuronal heterotopy (almost 4% of total motor neurons) in the anterior white matter. The delayed disease progression was likely to maintain fair motor activity despite a dramatic loss of large motor neurons. This provides a wonderful tool to probe novel drugs finely tuning the survival of motor neurons. In fact, small therapeutic effects protracted over considerable time intervals (even more than a year) are expected to be magnified., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Recent literature demonstrated that exposure to excitatory amino acid in specific experimental conditions might produce a defect in the autophagy pathway. Such an effect was observed in motor neurons exposed chronically to glutamate agonists. On the other hand, it is well known that glutamate induces motor neuron death and this is supposed to play a key role in the physiopathology of motor neuron loss in amyotrophic lateral sclerosis (ALS). Similarly, a defective recruitment of autophagy was recently documented in ALS. In the present study we found that exposure of motor neurons to kainic acid produces intracellular changes associated with defective autophagy. In this experimental conditions, pharmacological activation of autophagy rescues the loss of motor neurons.

Ten seborrheic keratosis of acanthotic type have been observed by S.E.M. The morphological study could confirm the existence of two processes in the origin of the horny cysts which are peculiar to this affection. a) an extrafollicular process causes the involvement of groups of keratinocytes which, by assuming a vortex disposition, produce a concentric keratinization; b) a follicular process which causes an accentuated keratinization of the cells surrounding the epithelial sheath. This process was associated to the presence of multiple hairs a single follicle. Moreover, with higher magnification, it was possible to observe a great number of bacteria, yeasts and of particular alteration of the membrane which could be compared to changes in the tone filaments.