Hippocampal radial glial subtypes and their neurogenic potential in human fetuses and healthy and Alzheimer's disease adults

Neuropathological conditions might affect adult granulogenesis in the adult human dentate gyrus. However, radial glial cells (RGCs) have not been well characterized during human development and aging. We have previously described progenitor and neuronal layer establishment in the hippocampal pyramidal layer and dentate gyrus from embryonic life until mid-gestation. Here, we describe RGC subtypes in the hippocampus from 13 gestational weeks (GW) to mid-gestation and characterize their evolution and the dynamics of neurogenesis from mid-gestation to adulthood in normal and Alzheimer's disease (AD) subjects. In the pyramidal ventricular zone (VZ), RGC density declined with neurogenesis from mid-gestation until the perinatal period. In the dentate area, morphologic and antigenic differences among RGCs were observed from early ages of development to adulthood. Density and proliferative capacity of dentate RGCs as well as neurogenesis were strongly reduced during childhood until 5 years, few DCX+ cells are seen in adults. The dentate gyrus of both control and AD individuals showed Nestin+ and/or GFAPδ+ cells displaying different morphologies. In conclusion, pools of morphologically, antigenically, and topographically diverse neural progenitor cells are present in the human hippocampus from early developmental stages until adulthood, including in AD patients, while their neurogenic potential seems negligible in the adult. Key words: adult neurogenesis, hippocampus, human fetal brain, neurogenesis, radial glial cell

Sex Differences in the Effects of Acute and Chronic Stress and Recovery after Long-Term Stress on Stress-Related Brain Regions of Rats

Studies show that sex plays a role in stress-related depression, with women experiencing a higher vulnerability to its effect. Two major targets of antidepressants are brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate response element–binding protein (CREB). The aim of this study was to investigate the levels of CREB, phosphorylation of CREB (pCREB), and BDNF in stress-related brain regions of male and female rats after stress and recovery. CREB and pCREB levels were examined in CA1, CA2, CA3, paraventricular nucleus of the thalamus (PVT), amygdala, anterior cingulate area, dorsal part (ACAd), and infralimbic area of prefrontal cortex (PFC), whereas dentate gyrus (DG) and prelimbic area (PL) of PFC were examined for BDNF levels. Our results demonstrate that levels of CREB and pCREB in male CA1, CA2 and CA3, PVT, amygdala, and ACAd were reduced by stress, whereas the same brain regions of female rats exhibited no change. BDNF levels were decreased by chronic stress in female PL but were increased by acute stress in female DG. BDNF levels in male DG and PL were found not to undergo change in response to stress. Abnormalities in morphology occurred after chronic stress in males but not in females. In all cases, the levels of CREB, pCREB, and BDNF in recovery animals were comparable to the levels of these proteins in control animals. These findings demonstrate a sexual dimorphism in the molecular response to stress and suggest that these differences may have important implications for potential therapeutic treatment of depression

Involvement of non-opioid peptides in the pathogenesis of neurological and psychiatric disorders: evidence from CSF and post-mortem studies

In the past twenty years, more than thirty peptides have been discovered to be present in the mammalian central nervous system (CNS). As the neuroanatomical distribution, neurochemical, electrophysiological and pharmacobehavioral effects of this novel group of neuroregulators have been described, it is evident that certain of these peptide-containing neural circuits may be pathologically altered in neuropsychiatric disorders. Although much attention has been focused on the opioid peptides, substantial data strongly support the hypothesis that non-opioid peptides such as somatostatin, neurotensin and substance P are altered in a diverse number of neuropsychiatric disorders including Alzheimer's disease, Huntington's chorea, Parkinson's disease, major depression and schizophrenia

Do neuropeptide systems mediate some of the effects of antipsychotic drugs?

Neuroleptic drugs are used in psychiatry for their antipsychotic actions. The current pharmacological hypothesis for their mechanism of action is largely based on the correlation between their potency to block dopamine (DA) receptors with their antipsychotic actions. Recently, the effect of chronic neuroleptic treatment on the concentrations of three neuropeptides, methionine-enkephalin (Met-ENK), cholecystokinin octapeptide (CCK-8) and neurotensin (NT), has been studied. These data are reviewed and evaluated in light of the possibility that neuroleptic drug action may be mediated, in part, through alterations in neuropeptide systems

Neurotensin-dopamine interactions: relevance to schizophrenia and the action of antipsychotic drugs

Despite the considerable data generated thus far, a unifying theory for the role(s) of NT in the CNS has not been achieved. However, several conclusions with clinical relevance can be made about neurotensin. First, NT is intimately associated with the mesolimbic DA system and has the ability to selectively modulate this system. Second, NT possesses a pharmacobehavioral profile that is similar to antipsychotic drugs, with many similarities to the atypical class of antipsychotics drugs. If the pathogenesis of schizophrenia is related to dopaminergic hyperactivity, then the existence of an endogenous NT system that modulates the activity of the DA system, may represent a mechanism for the prevention of psychosis. The ability of the atypical antipsychotic drugs to effectively reduce the symptoms of schizophrenia does not depend entirely upon the blockade of D2 receptors, yet many of these drugs alter NT concentrations. The development of NT receptor agonists that can cross the blood brain barrier may prove valuable in the treatment of schizophrenia, while avoiding the liability of EPS and TD