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Abstract:Neuropsychiatric disorders, which are associated with stress hormone dysregulation, occurat different rates in men and women. Moreover, nowadays, preclinical and clinical evidence demonstratesthat sex and gender can lead to differences in stress responses that predispose males andfemales to different expressions of similar pathologies. In this curated review, we focus on what isknown about sex differences in classic mechanisms of stress response, such as glucocorticoid hormonesand corticotrophin-releasing factor (CRF), which are components of the hypothalamicpituitary-adrenal (HPA) axis. Then, we present sex differences in neurotransmitter levels, such as serotonin,dopamine, glutamate and GABA, as well as indices of neurodegeneration, such as amyloid βand Tau. Gonadal hormone effects, such as estrogens and testosterone, are also discussed throughoutthe review. We also review in detail preclinical data investigating sex differences caused by recentlyrecognizedregulators of stress and disease, such as the immune system, genetic and epigenetic mechanisms,as well neurosteroids. Finally, we discuss how understanding sex differences in stress responses,as well as in pharmacology, can be leveraged into novel, more efficacious therapeutics forall. Based on the supporting evidence, it is obvious that incorporating sex as a biological variable intopreclinical research is imperative for the understanding and treatment of stress-related neuropsychiatricdisorders, such as depression, anxiety and Alzheimer’s disease. 

Abstract Deficits in hippocampus‐dependent memory processes are common across psychiatric and neurodegenerative disorders such as depression, anxiety and Alzheimer's disease. Moreover, stress is a major environmental risk factor for these pathologies and it exerts detrimental effects on hippocampal functioning via the activation of hypothalamic–pituitary–adrenal (HPA) axis. The medial septum cholinergic neurons extensively innervate the hippocampus. Although, the cholinergic septohippocampal pathway (SHP) has long been implicated in learning and memory, its involvement in mediating the adaptive and maladaptive impact of stress on mnemonic processes remains less clear. Here, we discuss current research highlighting the contributions of cholinergic SHP in modulating memory encoding, consolidation and retrieval. Then, we present evidence supporting the view that neurobiological interactions between HPA axis stress response and cholinergic signalling impact hippocampal computations. Finally, we critically discuss potential challenges and opportunities to target cholinergic SHP as a therapeutic strategy to improve cognitive impairments in stress‐related disorders. We argue that such efforts should consider recent conceptualisations on the dynamic nature of cholinergic signalling in modulating distinct subcomponents of memory and its interactions with cellular substrates that regulate the adaptive stress response.