Neuroscience
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Gonadal hormones are becoming increasingly recognized for their effects on cognition. Estrogens, in particular, have received attention for their effects on learning and memory that rely upon the functioning of various brain regions. However, the impacts of androgens on cognition are relatively under investigated. ⋯ We highlight the relevance of considering not only the actions of the most commonly studied steroids (i.e., testosterone, 17β-estradiol, and dihydrotestosterone), but also that of their metabolites and precursors, which interact with a plethora of different receptors and signalling molecules, ultimately modulating behaviour. We point out that it is also essential to investigate the effects of androgens, their precursors and metabolites in females, as prior studies have mostly focused on males. Overall, a comprehensive analysis of the impact of steroids such as androgens on behaviour is fundamental for a full understanding of the neural mechanisms underlying social cognition, including that of humans.
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Years before Alzheimer's disease (AD) is diagnosed, patients experience an impaired sense of smell, and β-amyloid plaques accumulate within the olfactory mucosa and olfactory bulb (OB). The olfactory vector hypothesis proposes that external agents cause β-amyloid to aggregate and spread from the OB to connected downstream brain regions. To reproduce the slow accumulation of β-amyloid that occurs in human AD, we investigated the progressive accumulation of β-amyloid across the brain using a conditional mouse model that overexpresses a humanized mutant form of the amyloid precursor protein (hAPP) in olfactory sensory neurons. ⋯ We also observe reduced OB volumes in these mice when hAPP expression begins prior-to but not post-weaning which we tracked using manganese-enhanced MRI. We therefore conclude that the reduced OB volume does not represent progressive degeneration but rather disrupted OB development. Overall, our data demonstrate that hAPP expression in the olfactory epithelium can lead to the accumulation and spread of β-amyloid through the olfactory system into the hippocampus, consistent with an olfactory system role in the early stages of β-amyloid-related AD progression.
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The unpredictable chronic mild stress (UCMS) model has been used to induce depressive-like symptoms in animal models, showing adequate predictive validity. Our work aims to evaluate the effects of environmental enrichment (EE) on resilience in this experimental model of depression. We also aim to assess changes in brain connectivity using cytochrome c oxidase histochemistry in cerebral regions related to cognitive-affective processes associated with depressive disorder: dorsal hippocampus, prefrontal cortex, amygdala, accumbens, and habenula nuclei. ⋯ EE induced a functional reorganization of brain activity. The EE + UCMS and UCMS groups showed different patterns of connections between brain regions. Our results showed that EE favors greater resilience and could reduce vulnerability to disorders such as depression and anxiety, modifying metabolic brain activity.
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Postoperative cognitive dysfunction (POCD) is characterized by impaired cognitive function, such as decreased learning and memory after anesthesia and surgery. This study aimed to explore the effect of luteoloside, a flavonoid extracted from natural herbs, on sevoflurane-induced cognitive dysfunction. Aged Sprague-Dawley male rats (20 months old) were treated with luteoloside for 7 days prior to sevoflurane exposure. ⋯ Notably, silencing Opa1 blocked the protective effect of luteoloside on hippocampal neurons and mitochondrial function. In summary, luteoloside prevented sevoflurane-induced cognitive dysfunction in aged rats, which may be achieved by regulating mitochondrial dynamics. Our study reveals the potential of luteoloside in preventing POCD in aged patients.
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Kainic acid (KA), an analogue of the excitatory neurotransmitter glutamate, when administered systemically can trigger seizures and neuronal loss in a manner that mirrors the neuropathology of human mesial temporal lobe epilepsy (mTLE), which affects ∼50 million people globally. Evidence suggests that changes in astrocytes which precede neuronal damage play an important role in the degeneration of neurons and/or development of seizures in TLE pathogenesis. Additionally, a role for microtubule associated tau protein, involved in various neurodegenerative diseases including Alzheimer's disease, has also been suggested in the development of seizure and/or neurodegeneration in TLE pathogenesis. ⋯ Concurrently, the total (Tau1 and Tau5) and phospho-tau (AT270 and PHF1) levels are transiently enhanced following KA administration. Furthermore, the level/expression of cleaved-tau, which is apparent in a subset of GFAP-, S100B- and A2-positive astrocytes, are increased in KA-treated rats. These results, taken together, suggest a differential role for various astrocytic subpopulations and tau protein in the development of seizure and/or loss of neurons in KA model of TLE and possibly in human mTLE pathogenesis.