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Developmental programing of thirst and sodium appetite

Mecawi AS, Macchione AF, Nuñez P, Perillan C, Reis LC, Vivas L, et al.

Neurosci Biobehav Rev, 2015 Apr;51:1-14.
PMID: 25528684 DOI: 10.1016/j.neubiorev.2014.12.012

Thirst and sodium appetite are the sensations responsible for the motivated behaviors of water and salt intake, respectively, and both are essential responses for the maintenance of hydromineral homeostasis in animals. These sensations and their related behaviors develop very early in the postnatal period in animals. Many studies have demonstrated several pre- and postnatal stimuli that are responsible for the developmental programing of thirst and sodium appetite and, consequently, the pattern of water and salt intake in adulthood in need-free or need-induced conditions. The literature systematically reports the involvement of dietary changes, hydromineral and cardiovascular challenges, renin-angiotensin system and steroid hormone disturbances, and lifestyle in these developmental factors. Therefore, this review will address how pre- and postnatal challenges can program lifelong thirst and sodium appetite in animals and humans, as well as which neuroendocrine substrates are involved. In addition, the possible epigenetic molecular mechanisms responsible for the developmental programing of drinking behavior, the clinical implications of hydromineral disturbances during pre- and postnatal periods, and the developmental origins of adult hydromineral behavior will be discussed.
From Kratom to mitragynine and its derivatives: physiological and behavioural effects related to use, abuse, and addiction

Hassan Z, Muzaimi M, Navaratnam V, Yusoff NH, Suhaimi FW, Vadivelu R, et al.

Neurosci Biobehav Rev, 2013 Feb;37(2):138-51.
PMID: 23206666 DOI: 10.1016/j.neubiorev.2012.11.012

Kratom (or Ketum) is a psychoactive plant preparation used in Southeast Asia. It is derived from the plant Mitragyna speciosa Korth. Kratom as well as its main alkaloid, mitragynine, currently spreads around the world. Thus, addiction potential and adverse health consequences are becoming an important issue for health authorities. Here we reviewed the available evidence and identified future research needs. It was found that mitragynine and M. speciosa preparations are systematically consumed with rather well defined instrumentalization goals, e.g. to enhance tolerance for hard work or as a substitute in the self-treatment of opiate addiction. There is also evidence from experimental animal models supporting analgesic, muscle relaxant, anti-inflammatory as well as strong anorectic effects. In humans, regular consumption may escalate, lead to tolerance and may yield aversive withdrawal effects. Mitragynine and its derivatives actions in the central nervous system involve μ-opioid receptors, neuronal Ca²⁺ channels and descending monoaminergic projections. Altogether, available data currently suggest both, a therapeutic as well as an abuse potential.
Dysregulation of the orexinergic system: A potential neuropeptide target in depression

Khairuddin S, Aquili L, Heng BC, Hoo TLC, Wong KH, Lim LW

Neurosci Biobehav Rev, 2020 11;118:384-396.
PMID: 32768489 DOI: 10.1016/j.neubiorev.2020.07.040

Orexins are highly involved in regulating the circadian rhythm, the brain's reward mechanism, and the neuroendocrine response to stress. The disruption of orexin regulation is known to be associated with depression. Preclinical studies in rodents have identified the dorsomedial/perifornical and lateral areas of the hypothalamus as the population of orexinergic neurons that are primarily responsible for mediating depression-induced neuroanatomical changes in the brain. There is still no consensus regarding whether hyperactivity or hypoactivity of orexin signaling is responsible for producing depressive-like behaviour. Likewise, clinical studies indicated a general disruption in orexin signaling in depressive patients, but did not report definitive evidence of either hyperactivity or hypoactivity. Nevertheless, given the various reciprocal connections between orexin neurons and multiple brain regions, it is plausible that this involves a differential signaling network with orexin neurons as the coordination center. Here, an overview of preclinical and clinical evidence is provided as a basis for understanding the consequences of altered orexin signaling on neural circuitries modulating different aspects of the physiopathology of depression.
ROCK2 inhibition: A futuristic approach for the management of Alzheimer's disease

Mani S, Jindal D, Chopra H, Jha SK, Singh SK, Ashraf GM, et al.

Neurosci Biobehav Rev, 2022 11;142:104871.
PMID: 36122738 DOI: 10.1016/j.neubiorev.2022.104871

Neurons depend on mitochondrial functions for membrane excitability, neurotransmission, and plasticity. Mitochondrial dynamics are important for neural cell maintenance. To maintain mitochondrial homeostasis, lysosomes remove dysfunctional mitochondria through mitophagy. Mitophagy promotes mitochondrial turnover and prevents the accumulation of dysfunctional mitochondria. In many neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), mitophagy is disrupted in neurons. Mitophagy is regulated by several proteins; recently, Rho-associated coiled-coil containing protein kinase 2 (ROCK2) has been suggested to negatively regulate the Parkin-dependent mitophagy pathway. Thus, ROCK2 inhibition may be a promising therapy for NDDs. This review summarizes the mitophagy pathway, the role of ROCK2 in Parkin-dependent mitophagy regulation, and mitophagy impairment in the pathology of AD. We further discuss different ROCK inhibitors (synthetic drugs, natural compounds, and gene therapy-based approaches) and examine their effects on triggering neuronal growth and neuroprotection in AD and other NDDs. This comprehensive overview of the role of ROCK in mitophagy inhibition provides a possible explanation for the significance of ROCK inhibitors in the therapeutic management of AD and other NDDs.
Fulltext The global prevalence of major depressive disorder (MDD) among the elderly: A systematic review and meta-analysis

Abdoli N, Salari N, Darvishi N, Jafarpour S, Solaymani M, Mohammadi M, et al.

Neurosci Biobehav Rev, 2022 Jan;132:1067-1073.
PMID: 34742925 DOI: 10.1016/j.neubiorev.2021.10.041

BACKGROUND: Major depressive disorder is characterized by a depressed mood or feeling of sadness, loss of interest or pleasure in everyday activities. Depressed individuals have a cognitive impairment, low self-esteem, difficulty making decisions, feeling helpless and hopeless. The factors that have been associated with depression include the lack of social support, living in rural areas, suffering from chronic diseases, smoking, and alcohol abuse. This study aimed to investigate the global prevalence of major depressive disorder in the elderly.
METHOD: The electronic database such as Web of Science (WoS), Scopus, SID, PubMed, Google Scholar, Mag Iran, and IranDoc were systematically searched for studies reporting the prevalence of major depressive disorderin the elderly published up to March 2021. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) software. Heterogeneity between the studies was evaluated using the I2 index. Begg and Mazumdar rank correlation test was used to assess publication bias.
RESULT: A total of 20 studies involving 18953 participants were included in this study. The global prevalence of major depression in the elderly was 13.3 % (95 % CI: 8.4-20.3 %). In the subgroup analysis, the prevalence of major depression in elderly women was 11.9 % (95 % CI: 7.6-18.6) and men 9.7 % (95 % CI: 5.2-17.3). No comparison was made between the two sexes, but based on the confidence intervals and large overlap, the two groups are not statistically different. Among continents, Australia had the highest prevalence of major depression in the elderly at 20.1 % (CI: 14.5-27.2 %). This was followed by Europe at 12.9 % (95 % CI: 5.1-28.9 %).
CONCLUSION: Major depressive disorder has a growing trend in the elderly population of the world. The prevalence of major depression in the elderly depends on various clinical and demographic factors such as age and gender. Therefore, mental health and the quality of life (QoL) of the elderly are important. The present study emphasizes the importance of social support in mental health that can reduce depression in the elderly.
Fulltext Habenula orphan G-protein coupled receptors in the pathophysiology of fear and anxiety

Roy N, Parhar I

Neurosci Biobehav Rev, 2022 Jan;132:870-883.
PMID: 34801259 DOI: 10.1016/j.neubiorev.2021.11.008

The phasic emotion, fear, and the tonic emotion, anxiety, have been conventionally inspected in clinical frameworks to epitomize memory acquisition, storage, and retrieval. However, inappropriate expression of learned fear in a safe environment and its resistance to suppression is a cardinal feature of various fear-related disorders. A significant body of literature suggests the involvement of extra-amygdala circuitry in fear disorders. Consistent with this view, the present review underlies incentives for the association between the habenula and fear memory. G protein-coupled receptors (GPCRs) are important to understand the molecular mechanisms central to fear learning due to their neuromodulatory role. The efficacy of a pharmacological strategy aimed at exploiting habenular-GPCR desensitization machinery can serve as a therapeutic target combating the pathophysiology of fear disorders. Originating from this milieu, the conserved nature of orphan GPCRs in the brain, with some having the highest expression in the habenula can lead to recent endeavors in understanding its functionality in fear circuitry.
Fulltext The effects of stimulant and non-stimulant medications on the autonomic nervous system (ANS) functioning in people with ADHD: A systematic review and meta-analysis

Idrees I, Bellato A, Cortese S, Groom MJ

Neurosci Biobehav Rev, 2023 Jan;144:104968.
PMID: 36427764 DOI: 10.1016/j.neubiorev.2022.104968

We carried out a systematic review and meta-analysis to investigate the effects of stimulant and non-stimulant medications on autonomic functioning in people with ADHD (PROSPERO: CRD42020212439). We searched (9th August 2021) PsycInfo, MEDLINE, EMBASE, Web of Science and The Cochrane Library, for randomised and non-randomised studies reporting indices of autonomic activity, (electrodermal, pupillometry and cardiac), pre- and post-medication exposure in people meeting DSM/ICD criteria for ADHD. In the narrative syntheses, we included 5 electrodermal studies, 1 pupillometry study and 57 studies investigating heart rate and blood pressure. In the meta-analyses, 29 studies were included on blood pressure and 32 on heart rate. Administration of stimulants, and to a lesser degree, non-stimulants increased heart rate and blood pressure in people with ADHD. Similarly, an upregulation of arousal, reflected in increased electrodermal activity and pupil diameter was observed following stimulant use. Yet, the methodological diversity of studies presented in this review reinforces the need for more standardised and rigorous research to fully understand the relationship between arousal, medication, and behaviour in ADHD.
Fulltext Anxiety, mood, and substance use disorders in adult men and women with and without attention-deficit/hyperactivity disorder: A substantive and methodological overview

Hartman CA, Larsson H, Vos M, Bellato A, Libutzki B, Solberg BS, et al.

Neurosci Biobehav Rev, 2023 Aug;151:105209.
PMID: 37149075 DOI: 10.1016/j.neubiorev.2023.105209

Knowledge on psychiatric comorbidity in adult ADHD is essential for prevention, detection, and treatment of these conditions. This review (1) focuses on large studies (n > 10,000; surveys, claims data, population registries) to identify (a) overall, (b) sex- and (c) age-specific patterns of comorbidity of anxiety disorders (ADs), major depressive disorder (MDD), bipolar disorder (BD) and substance use disorders (SUDs) in adults with ADHD relative to adults without ADHD; and (2) describes methodological challenges relating to establishing comorbidity in ADHD in adults as well as priorities for future research. Meta-analyses (ADHD: n = 550,748; no ADHD n = 14,546,814) yielded pooled odds ratios of 5.0(CI:3.29-7.46) for ADs, 4.5(CI:2.44-8.34) for MDD, 8.7(CI:5.47-13.89) for BD and 4.6(CI:2.72-7.80) for SUDs, indicating strong differences in adults with compared to adults without ADHD. Moderation by sex was not found: high comorbidity held for both men and women with sex-specific patterns as in the general population: higher prevalences of ADs, MDD and BD in women and a higher prevalence of SUDs in men. Insufficient data on different phases of the adult lifespan prevented conclusions on developmental changes in comorbidity. We discuss methodological challenges, knowledge gaps, and future research priorities.
Fulltext ATP-activated P2X7 receptor in the pathophysiology of mood disorders and as an emerging target for the development of novel antidepressant therapeutics

Wei L, Syed Mortadza SA, Yan J, Zhang L, Wang L, Yin Y, et al.

Neurosci Biobehav Rev, 2018 Apr;87:192-205.
PMID: 29453990 DOI: 10.1016/j.neubiorev.2018.02.005

Mood disorders are a group of psychiatric conditions that represent leading global disease burdens. Increasing evidence from clinical and preclinical studies supports that innate immune system dysfunction plays an important part in the pathophysiology of mood disorders. P2X7 receptor, belonging to the ligand-gated ion channel P2X subfamily of purinergic P2 receptors for extracellular ATP, is highly expressed in immune cells including microglia in the central nervous system (CNS) and has a vital role in mediating innate immune response. The P2X7 receptor is also important in neuron-glia signalling in the CNS. The gene encoding human P2X7 receptor is located in a locus of susceptibility to mood disorders. In this review, we will discuss the recent progress in understanding the role of the P2X7 receptor in the pathogenesis and development of mood disorders and in discovering CNS-penetrable P2X7 antagonists for potential uses in in vivo imaging to monitor brain inflammation and antidepressant therapeutics.
Structural and functional brain correlates of socioeconomic status across the life span: A systematic review

Thanaraju A, Marzuki AA, Chan JK, Wong KY, Phon-Amnuaisuk P, Vafa S, et al.

Neurosci Biobehav Rev, 2024 May 09;162:105716.
PMID: 38729281 DOI: 10.1016/j.neubiorev.2024.105716

It is well-established that higher socioeconomic status (SES) is associated with improved brain health. However, the effects of SES across different life stages on brain structure and function is still equivocal. In this systematic review, we aimed to synthesise findings from life course neuroimaging studies that investigated the structural and functional brain correlates of SES across the life span. The results indicated that higher SES across different life stages were independently and cumulatively related to neural outcomes typically reflective of greater brain health (e.g., increased cortical thickness, grey matter volume, fractional anisotropy, and network segregation) in adult individuals. The results also demonstrated that the corticolimbic system was most commonly impacted by socioeconomic disadvantages across the life span. This review highlights the importance of taking into account SES across the life span when studying its effects on brain health. It also provides directions for future research including the need for longitudinal and multimodal research that can inform effective policy interventions tailored to specific life stages.
Fulltext From neurons to brain networks, pharmacodynamics of stimulant medication for ADHD

Parlatini V, Bellato A, Murphy D, Cortese S

Neurosci Biobehav Rev, 2024 Sep;164:105841.
PMID: 39098738 DOI: 10.1016/j.neubiorev.2024.105841

Stimulants represent the first line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD) and are among the most prescribed psychopharmacological treatments. Their mechanism of action at synaptic level has been extensively studied. However, it is less clear how their mechanism of action determines clinically observed benefits. To help bridge this gap, we provide a comprehensive review of stimulant effects, with an emphasis on nuclear medicine and magnetic resonance imaging (MRI) findings. There is evidence that stimulant-induced modulation of dopamine and norepinephrine neurotransmission optimizes engagement of task-related brain networks, increases perceived saliency, and reduces interference from the default mode network. An acute administration of stimulants may reduce brain alterations observed in untreated individuals in fronto-striato-parieto-cerebellar networks during tasks or at rest. Potential effects of prolonged treatment remain controversial. Overall, neuroimaging has fostered understanding on stimulant mechanism of action. However, studies are often limited by small samples, short or no follow-up, and methodological heterogeneity. Future studies should address age-related and longer-term effects, potential differences among stimulants, and predictors of treatment response.

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