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Background: Aging is a complex and natural process. The physiological decline related to aging is accompanied by a slowdown in cognitive processes, which begins shortly after individuals reach maturity. These changes have been sometimes interpreted as a compensatory sign and others as a fingerprint of deterioration. Objective: In this context, our aim is to uncover the mechanisms that underlie and support normal cognitive functioning in the brain during the later stages of life. Methods: With this purpose, a systematic literature search was conducted using PubMed, Scopus, and Web of Science databases, which identified 781 potential articles. After applying inclusion and exclusion criteria, we selected 12 studies that examined the brain oscillations patterns in resting-state conditions associated with cognitive performance in cognitively unimpaired older adults. Results: Although cognitive healthy aging was characterized differently across studies, and various approaches to analyzing brain activity were employed, our review indicates a relationship between alpha peak frequency (APF) and improved performance in neuropsychological scores among cognitively unimpaired older adults. Conclusions: A higher APF is linked with a higher score in intelligence, executive function, and general cognitive performance, and could be considered an optimal, and easy-to-assess, electrophysiological marker of cognitive health in older adults.

Introduction: The increase in the incidence and prevalence of mental disorders in the university context is worrying, in addition to the tasks, demands and challenges of the educational system. Objective: To know the prevalence of psychopathological symptoms in university students. Method: 3831 adolescents and young adults, students from a public university in southern Peru, aged between 18 and 25 years, were evaluated. The study takes two phases: the first sampling phase, including a population of 26087 participants with a confidence level of 99%, and a margin of error of 2%. In this second phase, the random evaluation of 3821 subjects was carried out. The instruments used were the List of brief symptoms (LSB-50) and the Inventory of Anxiety Situations and Responses (ISRA). Results: Both tests showed significant differences in a variety of clinical subscales (p <0.05), women display moderate levels of depression, obsessioncompulsion, anxiety, and others. Besides, men show greater psychoreactivity and hostility. On the other hand, subjects younger than 23 years subject’s greater presence of psychopathology. Conclusion: The results show differences by sex and age. The early identification of psychopathological symptoms not only reduces the possibility of academic failure, but also substantially reduces other health risk behaviors, by promoting the well-being of university students., Introdução: O aumento da incidência e prevalência de transtornos mentais no contexto universitário é preocupante, considerando também as tarefas, exigências e desafios próprios do sistema educativo cada vez mais demandante. Objetivo: Conhecer a prevalência de sintomatologia psicopatológica em estudantes universitários. Método: Foram avaliados 3831 adolescentes e adultos jovens, estudantes de uma universidade pública ao sul do Peru, com idades entre 18 e 25 anos. O estudo se desenvolveu em duas fases: a primeira fase de amostra, incluiu uma população de 26087 participantes com um nível de confiança de 99% e uma margem de erro de 2%. Nessa segunda fase, foi realizada a avaliação aleatória de 3821 sujeitos. Os instrumentos utilizados foram: Listado de Síntomas breves (LSB-50) e o Inventario de Situações e Respostas de Ansiedade (ISRA); Resultados: Ambos os testes mostraram diferenças significativas em distintas subescalas clínicas (p<0.05). As mulheres mostraram maiores níveis de depressão, obsessão-compulsão, ansiedade e outros. Enquanto os homens tinham maior psicoreatividade e hostilidade. Por outro lado, os sujeitos menores de 23 anos de idade apresentaram maior presença de psicopatologia. Conclusão: Os resultados evidenciam diferenças por sexo e idade. A identificação precoce de sintomas psicopatológicos não somente minimizaria a possibilidade de fracasso acadêmico, como também reduziria em forma substancial outras condutas de risco para a saúde, através da promoção do bem-estar de estudantes universitários., Introducción: El incremento de la incidencia y prevalencia de trastornos mentales en el contexto universitario es preocupante, considerando además las tareas, exigencias y desafíos propios del sistema educativo cada vez más demandante. Objetivo: Conocer la prevalencia de sintomatología psicopatológica en estudiantes universitarios. Método: Se evaluaron 3831 adolescentes y adultos jóvenes, estudiantes de una universidad pública al sur del Perú, con edades entre 18 y 25 años. El estudio se desarrolló en dos fases; la primera fase de muestreo, incluyo una población de 26087 participantes con un nivel de confianza del 99%, y un margen de error del 2%. En esta segunda fase se realizó la evaluación aleatoria de 3821 sujetos. Los instrumentos utilizados fueron: El Listado de síntomas breves (LSB-50) y el Inventario de Situaciones y Respuestas de Ansiedad (ISRA). Resultados: Ambas pruebas mostraron diferencias significativas en distintas subescalas clínicas (p<0.05). Las mujeres mostraron mayores niveles de depresión, obsesión-compulsión, ansiedad y otros. Mientras que en los hombres tenían mayor psicorreactividad y hostilidad. Por otro lado, los sujetos menores a 23 años presentaron mayor presencia de psicopatología. Conclusión: Los resultados evidencian diferencias por sexo y edad. La identificación temprana de síntomas psicopatológicos no sólo minimizaría la posibilidad de fracaso académico, sino que también reduciría en forma substancial otras conductas de riesgo para la salud, a través de la promoción del bienestar de los estudiantes universitarios.

After decades of research in the neurobiology of IGF-I, its role as a prototypical neurotrophic factor is undisputed. However, many of its actions in the adult brain indicate that this growth factor is not only involved in brain development or in the response to injury. Following a three-layer assessment of its role in the central nervous system, we consider that at the cellular level, IGF-I is indeed a bona fide neurotrophic factor, modulating along ontogeny the generation and function of all the major types of brain cells, contributing to sculpt brain architecture and adaptive responses to damage. At the circuit level, IGF-I modulates neuronal excitability and synaptic plasticity at multiple sites, whereas at the system level, IGF-I intervenes in energy allocation, proteostasis, circadian cycles, mood, and cognition. Local and peripheral sources of brain IGF-I input contribute to a spatially restricted, compartmentalized, and timed modulation of brain activity. To better define these variety of actions, we consider IGF-I a modulator of brain states. This definition aims to reconcile all aspects of IGF-I neurobiology, and may provide a new conceptual framework in the design of future research on the actions of this multitasking neuromodulator in the brain.

Despite decades of intense research, disease-modifying therapeutic approaches for Alzheimer’s disease (AD) are still very much needed. Apart from the extensively analyzed tau and amyloid pathological cascades, two promising avenues of research that may eventually identify new druggable targets for AD are based on a better understanding of the mechanisms of resilience and vulnerability to this condition. We argue that insulin-like growth factor I (IGF-I) activity in the brain provides a common substrate for the mechanisms of resilience and vulnerability to AD. We postulate that preserved brain IGF-I activity contributes to resilience to AD pathology as this growth factor intervenes in all the major pathological cascades considered to be involved in AD, including metabolic impairment, altered proteostasis, and inflammation, to name the three that are considered to be the most important ones. Conversely, disturbed IGF-I activity is found in many AD risk factors, such as old age, type 2 diabetes, imbalanced diet, sedentary life, sociality, stroke, stress, and low education, whereas the Apolipoprotein (Apo) E4 genotype and traumatic brain injury may also be influenced by brain IGF-I activity. Accordingly, IGF-I activity should be taken into consideration when analyzing these processes, while its preservation will predictably help prevent the progress of AD pathology. Thus, we need to define IGF-I activity in all these conditions and develop a means to preserve it. However, defining brain IGF-I activity cannot be solely based on humoral or tissue levels of this neurotrophic factor, and new functionally based assessments need to be developed.

Sleep disturbances are common during aging. Compared to young animals, old mice show altered sleep structure, with changes in both slow and fast electrocorticographic (ECoG) activity and fewer transitions between sleep and wake stages. Insulin-like growth factor I (IGF-I), which is involved in adaptive changes during aging, was previously shown to increase ECoG activity in young mice and monkeys. Furthermore, IGF-I shapes sleep architecture by modulating the activity of mouse orexin neurons in the lateral hypothalamus (LH). We now report that both ECoG activation and excitation of orexin neurons by systemic IGF-I are abrogated in old mice. Moreover, orthodromical responses of LH neurons are facilitated by either systemic or local IGF-I in young mice, but not in old ones. As orexin neurons of old mice show dysregulated IGF-I receptor (IGF-IR) expression, suggesting disturbed IGF-I sensitivity, we treated old mice with AIK3a305, a novel IGF-IR sensitizer, and observed restored responses to IGF-I and rejuvenation of sleep patterns. Thus, disturbed sleep structure in aging mice may be related to impaired IGF-I signaling onto orexin neurons, reflecting a broader loss of IGF-I activity in the aged mouse brain.

Background: Cognitive impairment and dementia may result from a combination of modifiable and nonmodifiable risk and protective factors, such as the environment, educational attainment, time devoted to cognitively stimulating activities, and physical activity. Objective: This study aimed to investigate the mediating role of sociodemographic characteristics and lifestyle factors in the years of education and cognitive performance in Peruvian adults. Methods: This cross-sectional study included 1,478 subjects assessed by Addenbrooke’s Cognitive Examination Revised (ACE-R). Using mediation models, we evaluated the mediation role of parents’ educational level, reading time (RT), and physical activity time (PAT) in the years of education (IYE) and cognitive performance. Results: People who reported having lived in an urban area during their childhood are estimated to have, on average, 2.085 years more formal education than those who lived in rural areas. In addition, 49% of cognitive performance scores are explained by the mediation effect of reading and physical activity time in the IYE. This implies that higher levels of education, mediated by RT and PAT per week, are 1.596 units associated with higher scores on the ACE-R. Conclusion: Despite the fact that nonmodifiable factors (i.e., childhood residence area, parents’ educational level) seem to exert an effect on older adults’ cognition, their influence is mediated by other factors that are indeed modifiable (i.e., reading time, physical activity engagement). In this sense, lifestyle changes could help prevent or decrease the risk of cognitive impairment and reduce the disease’s impact on vulnerable environments in Latin American and Caribbean countries.

Maladaptive coping behaviors are probably involved in post-traumatic stress disorders (PTSD), but underlying mechanisms are incompletely understood. We now report that mice lacking functional insulin-like growth factor I (IGF-I) receptors in orexin neurons of the lateral hypothalamus (Firoc mice) are unresponsive to the anxiolytic actions of IGF-I and develop PTSD-like behavior that is ameliorated by inhibition of orexin neurons. Conversely, systemic IGF-I treatment ameliorated PTSD-like behavior in a wild-type mouse model of PTSD (PTSD mice). Further, systemic IGF-I modified the GABA/Glutamate synaptic structure in orexin neurons of naïve wild-type mice by increasing the dephosphorylation of GABA(B) receptor subunit through inhibition of AMP-kinase (AMPK). Significantly, pharmacological inhibition of AMPK mimicked IGF-I, normalizing fear behavior in PTSD mice. Thus, we suggest that IGF-I enables coping behaviors by balancing E/I input onto orexin neurons in a context-dependent manner. These observations provide a novel therapeutic approach to PTSD through modulation of AMPK.

Aging is accompanied by a decline in cognition that can be due to a lower IGF-I level. We studied response facilitation induced in primary somatosensory (S1) cortical neurons by repetitive stimulation of whiskers in young and old mice. Layer 2/3 and 5/6 neurons were extracellularly recorded in young (≤ 6 months of age) and old (≥ 20 month of age) anesthetized mice. IGF-I injection in S1 cortex (10 nM; 0.2 µL) increased whisker responses in young and old animals. A stimulation train at 8 Hz induced a long-lasting response facilitation in only layer 2/3 neurons of young animals. However, all cortical neurons from young and old animals showed long-lasting response facilitation when IGF-I was applied in the S1 cortex. The reduction in response facilitation in old animals can be due to a reduction in the IGF-I receptors as was indicated by the immunohistochemistry study. Furthermore, a reduction in the performance of a whisker discrimination task was observed in old animals. In conclusion, our findings indicate that there is a reduction in the synaptic plasticity of S1 neurons during aging that can be recovered by IGF-I. Therefore, it opens the possibility of use IGF-I as a therapeutic tool to ameliorate the effects of heathy aging.

Insulin-like growth factor-I (IGF-I) signaling plays a key role in learning and memory processes. While the effects of IGF-I on neurons have been studied extensively, the involvement of astrocytes in IGF-I signaling and the consequences on synaptic plasticity and animal behavior remain unknown. We have found that IGF-I induces long-term potentiation (LTP) of the postsynaptic potentials that is caused by a long-term depression of inhibitory synaptic transmission in mice. We have demonstrated that this long-lasting decrease in the inhibitory synaptic transmission is evoked by astrocytic activation through its IGF-I receptors (IGF-IRs). We show that LTP not only increases the output of pyramidal neurons, but also favors the NMDAR-dependent LTP, resulting in the crucial information processing at the barrel cortex since specific deletion of IGF-IR in cortical astrocytes impairs the whisker discrimination task. Our work reveals a novel mechanism and functional consequences of IGF-I signaling on cortical inhibitory synaptic plasticity and animal behavior, revealing that astrocytes are key elements in these processes.

It is known that aging is frequently accompanied by a decline in cognition. Furthermore, aging is associated with lower serum IGF-I levels that may contribute to this deterioration. We studied the effect of IGF-I in neurons of the horizontal diagonal band of Broca (HDB) of young (≤6 months old) and old (≥20-month-old) mice to determine if changes in the response of these neurons to IGF-I occur along with aging. Local injection of IGF-I in the HDB nucleus increased their neuronal activity and induced fast oscillatory activity in the electrocorticogram (ECoG). Furthermore, IGF-I facilitated tactile responses in the primary somatosensory cortex elicited by air-puffs delivered in the whiskers. These excitatory effects decreased in old mice. Immunohistochemistry showed that cholinergic HDB neurons express IGF-I receptors and that IGF-I injection increased the expression of c-fos in young, but not in old animals. IGF-I increased the activity of optogenetically-identified cholinergic neurons in young animals, suggesting that most of the IGF-I-induced excitatory effects were mediated by activation of these neurons. Effects of aging were partially ameliorated by chronic IGF-I treatment in old mice. The present findings suggest that reduced IGF-I activity in old animals participates in age-associated changes in cortical activity.

Although sleep disturbances are common co-morbidities of metabolic diseases, the underlying processes linking both are not yet fully defined. Changes in the duration of sleep are paralleled by changes in the levels of insulin-like growth factor-I (IGF-I), an anabolic hormone that shows a circadian pattern in the circulation and activity-dependent entrance in the brain. However, the specific role, if any, of IGF-I in this universal homeostatic process remains poorly understood. We now report that the activity of orexin neurons, a discrete cell population in the lateral hypothalamus that is involved in the circadian sleep/wake cycle and arousal, is modulated by IGF-I. Furthermore, mice with blunted IGF-I receptor activity in orexin neurons have lower levels of orexin in the hypothalamus, show altered electro-corticographic patterns with predominant slow wave activity, and reduced onset-sleep latency. Collectively, these results extend the role in the brain of this pleiotropic growth factor to shaping sleep architecture through the regulation of orexin neurons. We speculate that poor sleep quality associated to diverse conditions may be related to disturbed brain IGF-I input to orexin neurons.