Neuroscience
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Spontaneous depolarizations around the core are a consistent feature of focal cerebral ischemia, but the associated regional hemodynamic changes are heterogeneous. We determined how the features of depolarizations relate to subsequent cerebral blood flow (CBF) changes in global forebrain ischemia. Forebrain ischemia was produced in halothane-anesthetized rats (n=13) by common carotid artery occlusion and hypovolemic hypotension. ⋯ Short, transient depolarizations did not generate clear CBF responses. Depolarizations during incomplete global ischemia occurred at the lower limit of CBF autoregulation, propagated similar to spreading depolarization (SD), and the hemodynamic responses indicated inverse neurovascular coupling. Similar to SDs associated with focal stroke, the propagating event can be persistent or transient.
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Hippocampus is one of the brain regions in which neuroplastic changes occur. Paradigms such as environmental enrichment (ENR) have been used to prevent or delay the neuroplastic changes of the hippocampus during aging. Here, we investigated the beneficial effects of ENR on dendritic spines and hippocampal neurogenesis in middle age Balb/c mice. ⋯ In addition, ENR increased the proportion of cells with more mature dendritic morphology and net hippocampal neurogenesis. Whole-hippocampus protein extracts revealed that ENR increases the levels of BDNF, phospho-Akt and phospho-MAPK1/2, suggesting that the positive effects of ENR on neuroplasticity in middle age Balb/c mice involve the participation of these key-signaling proteins. Our results suggest that ENR is a relevant strategy to prevent neuroplastic decline by increasing the formation of both dendritic spines and new neurons in the hippocampus during middle age.
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The neuropeptide vasopressin (AVP; arginine-vasopressin) is produced in a handful of brain nuclei located in the hypothalamus and extended amygdala and is released both peripherally as a hormone and within the central nervous system as a neurotransmitter. Central projections have been associated with a number of functions including regulation of physiological homeostasis, control of circadian rhythms, and modulation of social behavior. The AVP neurons located in the bed nucleus of the stria terminalis and medial amygdala (i.e., extended amygdala) in particular have been associated with affiliative social behavior in multiple species. ⋯ Our data suggest that AVP had an excitatory influence on serotonin neurons. This work highlights a new target (i.e., V1AR) for manipulating serotonin neuron excitability. In light of our data, we propose that some of the diverse effects of AVP on physiology and behavior, including social behavior, may be due to activation of the DR serotonin system.
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The 5-HT (5-hydroxytryptamine) system has been assigned a key role in the development of 3,4-dihydroxyphenyl-l-alanine (l-DOPA)-induced dyskinesia, mainly due to 5-HT neuronal ability to decarboxylate l-DOPA into dopamine. Nevertheless, knowledge of l-DOPA-induced events that could lead to development of dyskinesias are limited and therefore the present work has evaluated (i) the role of the 5-HT system in l-DOPA-derived dopamine synthesis when dopamine neurons are present, (ii) l-DOPA-induced effects on striatal dopamine release and clearance, and on 5-HT nerve fiber density, and (iii) the behavioral outcome of altered 5-HT transmission in dyskinetic rats. Chronoamperometric recordings demonstrated attenuated striatal l-DOPA-derived dopamine release (∼30%) upon removal of 5-HT nerve fibers in intact animals. ⋯ Moreover, chronic l-DOPA exposure attenuated striatal 5-HT nerve fiber density in the absence of dopamine nerve terminals. Furthermore, fluoxetine-induced altered 5-HT transmission blocked dyskinetic behavior via action on 5-HT1A receptors. Taken together, the results indicate a central role for the 5-HT system in l-DOPA-derived dopamine synthesis and in dyskinesia, and therefore potential l-DOPA-induced deterioration of 5-HT function might reduce l-DOPA efficacy as well as promote the upcoming of motor side effects.
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Brain injury due to neonatal hypoxia-ischemia (HI) is more homogenously severe in male than in female mice. Because, necrostatin-1 (nec-1) prevents injury progression only in male mice, we hypothesized that changes in brain-derived neurotrophic factor (BDNF) signaling after HI and nec-1 are also sex-specific providing differential conditions to promote recovery of those more severely injured. The increased aromatization of testosterone in male mice during early development and the link between 17-β-estradiol (E2) levels and BDNF transcription substantiate this hypothesis. ⋯ Neonatal HI produces sex-specific signaling changes in the BDNF system, that are differentially modulated by nec-1. The regional differences in BDNF levels may be a consequence of injury severity after HI, but sexual differences in response to nec-1 after HI may represent a differential thalamo-cortical preservation or alternatively off-target regional effect of nec-1. The biological significance of ERα predominance and its correlation with BDNF levels is still unclear.