INTRODUCTION: Many studies support the notion that neuroinflammation involving glial cells may be... more INTRODUCTION: Many studies support the notion that neuroinflammation involving glial cells may be the fundamental pathogenic event that lead to brain damage and degeneration in Alzheimer’s disease (AD). The effects of minocycline on glial cells activation in the lipopolysaccharide (LPS) rat model is studied here. MATERIALS AND METHODS: Fifty adult male Sprague Dawley rats were split into five groups: control, LPS, LPS-treated with minocycline 25 mg/kg, LPS-treated with minocycline 50 mg/kg, and LPS treated with memantine 10 mg/kg. For two weeks, rats were treated with minocycline and memantine intraperitoneally daily, while were injected with LPS intraperitoneally once on day 5. Morris water maze (MWM) test was performed to evaluate the learning and working memory behaviour. Immunohistochemistry and Western blot were performed to measure ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) expressions in the hippocampal tissue. RESULTS: LPS i...
Background: Lesion studies have shown distinct roles for the hippocampus, with the dorsal subregi... more Background: Lesion studies have shown distinct roles for the hippocampus, with the dorsal subregion being involved in processing of spatial information and memory, and the ventral aspect coding for emotion and motivational behaviour. However, its structural connectivity with the subdivisions of the prefrontal cortex (PFC), the executive area of the brain that also has various distinct functions, has not been fully explored, especially in the Malaysian population. Methods: We performed diffusion magnetic resonance imaging with probabilistic tractography on four Malay males to parcellate the hippocampus according to its relative connection probability to the six subdivisions of the PFC. Results: Our findings revealed that each hippocampus showed putative connectivity to all the subdivisions of PFC, with the highest connectivity to the orbitofrontal cortex (OFC). Parcellation of the hippocampus according to its connection probability to the six PFC subdivisions showed variability in th...
Neuroinflammation following lipopolysaccharide (LPS) administration induces locomotor deficits an... more Neuroinflammation following lipopolysaccharide (LPS) administration induces locomotor deficits and anxiety-like behaviour. In this study, minocycline was compared to memantine, an NMDA receptor antagonist, for its effects on LPS-induced locomotor deficits and anxiety-like behaviour in rats. Adult male Sprague Dawley rats were administered either two different doses of minocycline (25 or 50 mg/kg/day, i.p.) or 10 mg/kg/day of memantine (i.p.) for 14 days four days prior to an LPS (5 mg/kg, i.p.) injection. Locomotor activity and anxiety-like behaviour were assessed using the open-field test (OFT). The phosphorylated tau protein level was measured using ELISA, while the expression and density of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding (CREB) protein in the medial prefrontal cortex (mPFC) were measured using immunohistochemistry and Western blot, respectively. Minocycline treatment reduced locomotor deficits and anxiety-like behaviour associated with ...
Sleep disturbances and disruptions of circadian rhythms are underlying factors in most mood disor... more Sleep disturbances and disruptions of circadian rhythms are underlying factors in most mood disorders like major depressive disorder (MDD) and bipolar disorder (BD), and their seasonal pattern or seasonal affective disorder (SAD). Decreases in sleep efficiency, total sleep time and sleep quality have all been documented in MDD. In addition to this, depressed patients of all these three categories (MDD, BD, SAD) exhibit profound disturbances in circadian rhythms including the sleep-wake rhythm. Circadian clock dysregulation has been suggested to be due abnormal circadian rhythmicity of gene expression. In particular, CRY1 and CRY2 polymorphisms have been shown to be associated with MDD. Similarly, variations in CRY2, PER2, ARNTL and NPAS2 are associated with SAD. An antidepressant that benefits sleep quality and resynchronize disrupted circadian rhythms will be most useful in treating mood disorders. In this context, the newly introduced melatonergic antidepressant agomelatine with M...
Recent interest in multiple sclerosis research warrants literature analysis to evaluate the curre... more Recent interest in multiple sclerosis research warrants literature analysis to evaluate the current state of the discipline and new research domains. This bibliometric review summarised the research trends and analysed research areas in multiple sclerosis over the last decade. The documents containing the term ‘multiple sclerosis’ in the article title were retrieved from the Scopus database. We used Harzing’s Publish or Perish and VOSviewer for citation analysis and data visualisation, respectively. We found a total of 18,003 articles published in journals in the English language between 2012 and 2021. The emerging keywords identified utilising the enhanced strategic diagram were ‘covid-19’, ‘teriflunomide’, ‘clinical trial’, ‘microglia’, ‘b cells’, ‘myelin’, ‘brain’, ‘white matter’, ‘functional connectivity’, ‘pain’, ‘employment’, ‘health-related quality of life’, ‘meta-analysis’ and ‘comorbidity’. This study demonstrates the tremendous growth of multiple sclerosis literature world...
Introduction: Electroconvulsive therapy (ECT) has been widely accepted as among the most effectiv... more Introduction: Electroconvulsive therapy (ECT) has been widely accepted as among the most effective therapeutic methods for major depressive disorder (MDD) or schizophrenia patients who show poor response to standard pharmacological treatment. One of the adverse effects of ECT which remains controversial is cognitive impairment. Methods: In this article, we review the available literature about pharmacological agents that could prevent the cognitive adverse effects of ECT. Results: Among the agents that have been shown to prevent cognitive adverse effects of ECT in humans include piracetam, naloxone, anesthetic agents, anticholinesterase drugs, memantine, thyroid hormones, and a combination of herbs. Conclusion: While preventing the cognitive adverse effects of ECT is currently not attainable, using pharmacological agents/herbs have been found to confer beneficial effects in reducing cognitive impairment.
Background: Tualang honey has been shown to reduce oxidative stress in various animal models. Obj... more Background: Tualang honey has been shown to reduce oxidative stress in various animal models. Objective: This study aims to investigate the responses of antioxidant defenses to normobaric hypoxia and the effects of Tualang honey on brain oxidant/antioxidant status of adult male rats. Methods: The rats were divided into four groups (n = 12 per group); i) sucrose non-hypoxia, ii) sucrose with hypoxia, iii) honey non-hypoxia, iv) honey with hypoxia. Oral Tualang honey (0.2 g/kg body weight) and sucrose (1 mL of 7.9%) supplementations were given to the rats daily for 14 days. The rats were then subjected to ~11% continuous normobaric hypoxia for 7 days. The brain homogenate was used to determine oxidative stress markers levels/activities. Results: The sucrose with hypoxia group demonstrated a significant increase in malondialdehyde (MDA) and a decrease in total antioxidant capacity (TAC), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels when compared to...
Background: Recently published findings noted that women suffer from Alzheimer disease, a form of... more Background: Recently published findings noted that women suffer from Alzheimer disease, a form of neurodegenerative disorder, more often than men, even accounting for the fact that women on average live longer. Objective: Menopause rodent model may be an invaluable tool for assessing longitudinal effects of hormones and aging, as well as providing access to body tissues especially brain, from which insight into the mechanisms related to cognitive aging and Alzheimer disease can be gleaned. Method: This review highlights the suitability and limitations of using menopause rodent models for cognitive aging research. Conclusion: Intact aging and OVX animals mimic natural and surgical menopause, respectively, hence making them suitable menopause models for cognitive aging research after taking into account their limitations.
Aging is associated with a variety of morphological and functional changes in the liver. Oxidativ... more Aging is associated with a variety of morphological and functional changes in the liver. Oxidative stress and inflammation are now widely accepted as the main mechanisms involved in the aging process that may subsequently cause severe injury to mitochondrial DNA which leads to apoptosis. As aging may increase the risks for various liver diseases and plays as an adverse prognostic factor increasing the mortality rate, knowledge regarding the mechanisms of age-related liver susceptibility and the possible therapeutic interventions is imperative. Due to cost and time constraints, a mimetic aging model is generally preferred to naturally aged animals to study the underlying mechanisms of aging liver. The use of D-galactose in aging research is dated back to 1962 and has since been used widely. This review aims to comprehensively summarize the effects of D-galactose-induced aging on the liver and the underlying mechanisms involved. Its potential therapeutic interventions are also discussed. It is hoped that this invaluable information may facilitate researchers in choosing the appropriate aging model and provide a valuable platform for testing potential therapeutic strategies for the prevention and treatment of age-related liver diseases.
Tualang honey has been shown to protect against neurodegeneration, leading to improved memory/lea... more Tualang honey has been shown to protect against neurodegeneration, leading to improved memory/learning as well as mood. In addition, studies have also demonstrated its anti-inflammatory and antioxidant properties. However, a substantial part of this research lacks systematization, and there seems to be a tendency to start anew with every study. This review presents a decade of research on Tualang honey with a particular interest in the underlying mechanisms related to its effects on the central nervous system. A total of 28 original articles published between 2011 and 2020 addressing the central nervous system (CNS) effects of Tualang honey were analysed. We identified five main categories, namely nootropic, antinociceptive, stress-relieving, antidepressant, and anxiolytic effects of Tualang honey, and proposed the underlying mechanisms. The findings from this review may potentially be beneficial towards developing new therapeutic roles for Tualang honey and help in determining how ...
Abstract Hypoxia has been associated with cognitive impairment. Many studies have investigated th... more Abstract Hypoxia has been associated with cognitive impairment. Many studies have investigated the role of mTOR signalling pathway in cognitive functions but its role in hypoxia-induced cognitive impairment remains controversial. This review aimed to elucidate the role of mTOR in the mechanisms of cognitive impairment that may pave the way towards the mechanistic understanding and therapeutic intervention of hypoxia-induced cognitive impairment. mTORC1 is normally regulated during mild or acute hypoxic exposure giving rise to neuroprotection, whereas it is overactivated during severe or chronic hypoxia giving rise to neuronal cells death. Thus, it is worth exploring the possibility of maintaining normal mTORC1 activity and thereby preventing cognitive impairment during severe or chronic hypoxia.
INTRODUCTION: Many studies support the notion that neuroinflammation involving glial cells may be... more INTRODUCTION: Many studies support the notion that neuroinflammation involving glial cells may be the fundamental pathogenic event that lead to brain damage and degeneration in Alzheimer’s disease (AD). The effects of minocycline on glial cells activation in the lipopolysaccharide (LPS) rat model is studied here. MATERIALS AND METHODS: Fifty adult male Sprague Dawley rats were split into five groups: control, LPS, LPS-treated with minocycline 25 mg/kg, LPS-treated with minocycline 50 mg/kg, and LPS treated with memantine 10 mg/kg. For two weeks, rats were treated with minocycline and memantine intraperitoneally daily, while were injected with LPS intraperitoneally once on day 5. Morris water maze (MWM) test was performed to evaluate the learning and working memory behaviour. Immunohistochemistry and Western blot were performed to measure ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) expressions in the hippocampal tissue. RESULTS: LPS i...
Background: Lesion studies have shown distinct roles for the hippocampus, with the dorsal subregi... more Background: Lesion studies have shown distinct roles for the hippocampus, with the dorsal subregion being involved in processing of spatial information and memory, and the ventral aspect coding for emotion and motivational behaviour. However, its structural connectivity with the subdivisions of the prefrontal cortex (PFC), the executive area of the brain that also has various distinct functions, has not been fully explored, especially in the Malaysian population. Methods: We performed diffusion magnetic resonance imaging with probabilistic tractography on four Malay males to parcellate the hippocampus according to its relative connection probability to the six subdivisions of the PFC. Results: Our findings revealed that each hippocampus showed putative connectivity to all the subdivisions of PFC, with the highest connectivity to the orbitofrontal cortex (OFC). Parcellation of the hippocampus according to its connection probability to the six PFC subdivisions showed variability in th...
Neuroinflammation following lipopolysaccharide (LPS) administration induces locomotor deficits an... more Neuroinflammation following lipopolysaccharide (LPS) administration induces locomotor deficits and anxiety-like behaviour. In this study, minocycline was compared to memantine, an NMDA receptor antagonist, for its effects on LPS-induced locomotor deficits and anxiety-like behaviour in rats. Adult male Sprague Dawley rats were administered either two different doses of minocycline (25 or 50 mg/kg/day, i.p.) or 10 mg/kg/day of memantine (i.p.) for 14 days four days prior to an LPS (5 mg/kg, i.p.) injection. Locomotor activity and anxiety-like behaviour were assessed using the open-field test (OFT). The phosphorylated tau protein level was measured using ELISA, while the expression and density of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding (CREB) protein in the medial prefrontal cortex (mPFC) were measured using immunohistochemistry and Western blot, respectively. Minocycline treatment reduced locomotor deficits and anxiety-like behaviour associated with ...
Sleep disturbances and disruptions of circadian rhythms are underlying factors in most mood disor... more Sleep disturbances and disruptions of circadian rhythms are underlying factors in most mood disorders like major depressive disorder (MDD) and bipolar disorder (BD), and their seasonal pattern or seasonal affective disorder (SAD). Decreases in sleep efficiency, total sleep time and sleep quality have all been documented in MDD. In addition to this, depressed patients of all these three categories (MDD, BD, SAD) exhibit profound disturbances in circadian rhythms including the sleep-wake rhythm. Circadian clock dysregulation has been suggested to be due abnormal circadian rhythmicity of gene expression. In particular, CRY1 and CRY2 polymorphisms have been shown to be associated with MDD. Similarly, variations in CRY2, PER2, ARNTL and NPAS2 are associated with SAD. An antidepressant that benefits sleep quality and resynchronize disrupted circadian rhythms will be most useful in treating mood disorders. In this context, the newly introduced melatonergic antidepressant agomelatine with M...
Recent interest in multiple sclerosis research warrants literature analysis to evaluate the curre... more Recent interest in multiple sclerosis research warrants literature analysis to evaluate the current state of the discipline and new research domains. This bibliometric review summarised the research trends and analysed research areas in multiple sclerosis over the last decade. The documents containing the term ‘multiple sclerosis’ in the article title were retrieved from the Scopus database. We used Harzing’s Publish or Perish and VOSviewer for citation analysis and data visualisation, respectively. We found a total of 18,003 articles published in journals in the English language between 2012 and 2021. The emerging keywords identified utilising the enhanced strategic diagram were ‘covid-19’, ‘teriflunomide’, ‘clinical trial’, ‘microglia’, ‘b cells’, ‘myelin’, ‘brain’, ‘white matter’, ‘functional connectivity’, ‘pain’, ‘employment’, ‘health-related quality of life’, ‘meta-analysis’ and ‘comorbidity’. This study demonstrates the tremendous growth of multiple sclerosis literature world...
Introduction: Electroconvulsive therapy (ECT) has been widely accepted as among the most effectiv... more Introduction: Electroconvulsive therapy (ECT) has been widely accepted as among the most effective therapeutic methods for major depressive disorder (MDD) or schizophrenia patients who show poor response to standard pharmacological treatment. One of the adverse effects of ECT which remains controversial is cognitive impairment. Methods: In this article, we review the available literature about pharmacological agents that could prevent the cognitive adverse effects of ECT. Results: Among the agents that have been shown to prevent cognitive adverse effects of ECT in humans include piracetam, naloxone, anesthetic agents, anticholinesterase drugs, memantine, thyroid hormones, and a combination of herbs. Conclusion: While preventing the cognitive adverse effects of ECT is currently not attainable, using pharmacological agents/herbs have been found to confer beneficial effects in reducing cognitive impairment.
Background: Tualang honey has been shown to reduce oxidative stress in various animal models. Obj... more Background: Tualang honey has been shown to reduce oxidative stress in various animal models. Objective: This study aims to investigate the responses of antioxidant defenses to normobaric hypoxia and the effects of Tualang honey on brain oxidant/antioxidant status of adult male rats. Methods: The rats were divided into four groups (n = 12 per group); i) sucrose non-hypoxia, ii) sucrose with hypoxia, iii) honey non-hypoxia, iv) honey with hypoxia. Oral Tualang honey (0.2 g/kg body weight) and sucrose (1 mL of 7.9%) supplementations were given to the rats daily for 14 days. The rats were then subjected to ~11% continuous normobaric hypoxia for 7 days. The brain homogenate was used to determine oxidative stress markers levels/activities. Results: The sucrose with hypoxia group demonstrated a significant increase in malondialdehyde (MDA) and a decrease in total antioxidant capacity (TAC), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels when compared to...
Background: Recently published findings noted that women suffer from Alzheimer disease, a form of... more Background: Recently published findings noted that women suffer from Alzheimer disease, a form of neurodegenerative disorder, more often than men, even accounting for the fact that women on average live longer. Objective: Menopause rodent model may be an invaluable tool for assessing longitudinal effects of hormones and aging, as well as providing access to body tissues especially brain, from which insight into the mechanisms related to cognitive aging and Alzheimer disease can be gleaned. Method: This review highlights the suitability and limitations of using menopause rodent models for cognitive aging research. Conclusion: Intact aging and OVX animals mimic natural and surgical menopause, respectively, hence making them suitable menopause models for cognitive aging research after taking into account their limitations.
Aging is associated with a variety of morphological and functional changes in the liver. Oxidativ... more Aging is associated with a variety of morphological and functional changes in the liver. Oxidative stress and inflammation are now widely accepted as the main mechanisms involved in the aging process that may subsequently cause severe injury to mitochondrial DNA which leads to apoptosis. As aging may increase the risks for various liver diseases and plays as an adverse prognostic factor increasing the mortality rate, knowledge regarding the mechanisms of age-related liver susceptibility and the possible therapeutic interventions is imperative. Due to cost and time constraints, a mimetic aging model is generally preferred to naturally aged animals to study the underlying mechanisms of aging liver. The use of D-galactose in aging research is dated back to 1962 and has since been used widely. This review aims to comprehensively summarize the effects of D-galactose-induced aging on the liver and the underlying mechanisms involved. Its potential therapeutic interventions are also discussed. It is hoped that this invaluable information may facilitate researchers in choosing the appropriate aging model and provide a valuable platform for testing potential therapeutic strategies for the prevention and treatment of age-related liver diseases.
Tualang honey has been shown to protect against neurodegeneration, leading to improved memory/lea... more Tualang honey has been shown to protect against neurodegeneration, leading to improved memory/learning as well as mood. In addition, studies have also demonstrated its anti-inflammatory and antioxidant properties. However, a substantial part of this research lacks systematization, and there seems to be a tendency to start anew with every study. This review presents a decade of research on Tualang honey with a particular interest in the underlying mechanisms related to its effects on the central nervous system. A total of 28 original articles published between 2011 and 2020 addressing the central nervous system (CNS) effects of Tualang honey were analysed. We identified five main categories, namely nootropic, antinociceptive, stress-relieving, antidepressant, and anxiolytic effects of Tualang honey, and proposed the underlying mechanisms. The findings from this review may potentially be beneficial towards developing new therapeutic roles for Tualang honey and help in determining how ...
Abstract Hypoxia has been associated with cognitive impairment. Many studies have investigated th... more Abstract Hypoxia has been associated with cognitive impairment. Many studies have investigated the role of mTOR signalling pathway in cognitive functions but its role in hypoxia-induced cognitive impairment remains controversial. This review aimed to elucidate the role of mTOR in the mechanisms of cognitive impairment that may pave the way towards the mechanistic understanding and therapeutic intervention of hypoxia-induced cognitive impairment. mTORC1 is normally regulated during mild or acute hypoxic exposure giving rise to neuroprotection, whereas it is overactivated during severe or chronic hypoxia giving rise to neuronal cells death. Thus, it is worth exploring the possibility of maintaining normal mTORC1 activity and thereby preventing cognitive impairment during severe or chronic hypoxia.
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