Neuroscience
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The recombinant C-terminal domain of tetanus toxin (Hc-TeTx) is a new non-toxic peptide of the tetanus toxin that exerts a protective action against glutamate excitotoxicity in motoneurons. Moreover, its efficacy as a neuroprotective agent has been demonstrated in several animal models of neurodegeneration. The eleven amino acids in the β amyloid peptide (Aβ25-35) mimic the toxic effects of the full β amyloid peptide (Aβ1-42), causing the impairment of the cholinergic system in the medial septum (MS) which, in turn, alters the septo-hippocampal pathway and leads to learning and memory impairments. ⋯ All these improvements were reflected in spatial learning and memory performance, and were significantly higher compared with animals treated with Aβ(25-35). Interestingly, the single administration of Hc-TeTx into the MS modified the ChAT and AChE expression that affect cognitive processes, without inducing neurodegeneration or an increase in capase-3 expression in the MS and hippocampus. In summary, our findings suggest that the recombinant Hc-TeTx fragment offers effective protection for the septo-hippocampal pathway, given that it reduces the neurodegeneration caused by Aβ(25-35) and improves learning and memory processes.
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Syrian hamsters exposed to anabolic/androgenic steroids (AAS) during adolescence consistently show increased aggressive behavior across studies. Although the behavioral and anatomical profiles of AAS-induced alterations have been well characterized, there is a lack of data describing physiological changes that accompany these alterations. For instance, behavioral pharmacology and neuroanatomical studies show that AAS-induced changes in the vasopressin (AVP) neural system within the latero-anterior hypothalamus (LAH) interact with the serotonin (5HT) and dopamine (DA) systems to modulate aggression. ⋯ Both DA D2 antagonists and 5HT increased the firing frequency of AVP-responsive cells from AAS animals and dual application of AVP and D2 antagonists doubled the excitatory effect of AVP or D2 antagonist administration alone. These data suggest that multiple DA circuits in the LAH modulate AAS-induced aggressive responding. More broadly, these data show that multiple neurochemical interactions at the neurophysiological level are altered by adolescent AAS exposure.
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Obesity and type 2 diabetes mellitus (T2DM) convey an increased risk for developing dementia. The microtubule-associated protein tau is implicated in neurodegenerative disease by undergoing hyperphosphorylation and aggregation, leading to cytotoxicity and neurodegeneration. Enzymes involved in the regulation of tau phosphorylation, such as GSK3β, are tightly associated with pathways found to be dysregulated in T2DM. ⋯ The resulting phenotype included a striking increase in tau phosphorylation and the number of neurofibrillary tangles (NFTs) found within the hippocampus. We conclude that leptin resistance-induced obesity and diabetes accelerates the development of tau pathology. This model of metabolic dysfunction and tauopathy provides a new system in which to explore the mechanisms underlying the ways in which leptin resistance and diabetes influence development of tau pathology, and may ultimately be related to the development of NFTs.
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Circadian rhythms in mammals are regulated by a system of circadian oscillators that includes a light-entrainable pacemaker in the suprachiasmatic nucleus (SCN) and food-entrainable oscillators (FEOs) elsewhere in the brain and body. In nocturnal rodents, the SCN promotes sleep in the day and wake at night, while FEOs promote an active state in anticipation of a predictable daily meal. For nocturnal animals to anticipate a daytime meal, wake-promoting signals from FEOs must compete with sleep-promoting signals from the SCN pacemaker. ⋯ Changes in either direction were concurrent with locomotion, were not specific to food anticipation, and were not sustained during longer pauses. Reduced FOS indicates a net suppression of SCN activity that may depend on the intensity or duration of locomotion. The timing of changes in SCN activity relative to locomotion suggests that any effect of FEOs on SCN output is mediated indirectly, by feedback from neural or systemic correlates of locomotion.
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High sugar consumption is a risk factor for metabolic disturbances leading to memory impairment. Thus, rats subject to high sucrose intake (HSu) develop a metabolic syndrome and display memory deficits. We now investigated if these HSu-induced memory deficits were associated with metabolic and electrophysiological alterations in the hippocampus. ⋯ HSu rats also displayed no change of synaptic transmission and plasticity (long-term potentiation) in hippocampal Schaffer fibers-CA1 pyramid synapses, but had decreased amplitude of long-term depression in the temporoammonic (TA) pathway. Furthermore, HSu rats had an increased density of inhibitory adenosine A1 receptors (A1R), that translated into a greater potency of A1R in Schaffer fiber synapses, but not in the TA pathway, whereas the endogenous activation of A1R in HSu rats was preserved in the TA pathway but abolished in Schaffer fiber synapses. These results suggest that HSu triggers a hippocampal-dependent memory impairment that is not associated with altered hippocampal metabolism but is probably related to modified synaptic plasticity in hippocampal TA synapses.