Journal: Journal of neuroscience research
The present study analyzed the in vitro effects induced by sodium L-lactate on human astrocytes and the SH-SY5Y cell line, when added at concentrations of 5, 10, and 25 mmol/liter. Expression of brain-derived neurotrophic factor (BDNF), inducible nitric oxide synthase (iNOS), and heat shock protein 70 kDa (HSP70) was evaluated by Western blot analysis. Cell viability with MTT, release of nitric oxide (NO) through the Griess reaction, and production of BDNF by enzyme-linked immunoassay was determined. Data indicate that, in SH-SY5Y as well as in cortical astrocytes, after 4 hr sodium L-lactate increases the expression and release of BDNF, iNOS, and NO; after 24 hr, it turns is ineffective for the production of the neurotrophin in SH-SY5Y and not in astrocytes, but the expression of iNOS and release of NO appear to be further increased compared with those after 4 hr. Sodium L-lactate influences differently the expression of HSP70 in SH-SY5Y compared with astrocytes. We propose, based on these findings, that sodium L-lactate affects the expression of BDNF in SH-SY5Y and astrocytes in a different manner: high levels of iNOS and NO expressed in SH-SY5Y have a profound inhibitory effect on the release of BDNF related to a more limited production of HSP70 by SH-SY5Y. In conclusion, the results demonstrate differences in the responses of SH-SY5Y and astrocytes to stimulation by high levels of sodium L-lactate. Sodium L-lactate differently and dose and time dependently influences the expression and release of BDNF, iNOS, NO, and HSP70 depending on the cell type. © 2012 Wiley Periodicals, Inc.
The amygdala contributes to the generation and propagation of epileptiform activity in temporal lobe epilepsy (TLE). Ictal symptoms such as fear, dreamy states (déjà vu, memory flashbacks, experiential hallucinations), epigastric auras, or sympathetic outflow with cardiovascular changes are often linked to a seizure focus in the amygdala. However, the amygdala may also play a role in comorbid anxiety, depression, and other psychiatric symptoms experienced in the interictal phase, especially in pharmacoresistant TLE. The few studies available on TLE-related alterations in surgical amygdala specimens indicate loss of both excitatory spiny projection neurons as well as interneurons in nuclei with a cortex-like architecture, which may influence mechanisms of feedforward and feedback inhibition. Studies of the human amygdala indicate global alterations in the density of AMPA/kainate, metabotropic glutamate, γ-aminobutyric acid type A (GABAA ), muscarinic M2 and M3, serotonergic 5-HT1A, and adrenergic α1 receptors. Also, amygdala GABAergic and neuropeptide Y (NPY) systems affected in human TLE are both involved in antiepileptic and anxiolytic effects. Experimental and human positron emission tomography studies indicate changes in amygdala serotonergic, NPY Y1 receptor, neurokinin, and opioid systems in emotional disturbances in TLE. Of particular interest is the reduction in amygdala volume in conjunction with ictal fear, seizure focus in the amygdala, and amygdala and hippocampal sclerosis in TLE patients. In contrast, patients with interictal depression often have an intact or even enlarged amygdala and a negative MRI associated with amygdala hypometabolism, which can be associated with limbic autoimmune encephalitis. These findings suggest a differential role of TLE-related amygdala changes in ictal and interictal emotional disturbances. © 2015 Wiley Periodicals, Inc.
Parkinson’s disease (PD) is one of the most common forms of neurodegenerative disease in the elderly population and is typically manifested by motor symptoms and nonmotor symptoms and signs. Nonmotor symptoms, such as sensory symptoms, have been regarded as the significant features of this disease. These symptoms often occur in early stages of PD and influence quality of life. However, researchers suggest that the sensory symptoms of PD are frequently unrecognized by clinicians and remain untreated. The disorders include pain, olfactory disturbance, and visual dysfunction input on the underlying sensory abnormality. This Review focuses on the clinical features, pathophysiological mechanisms, and treatment strategies for sensory symptoms of PD from both clinical studies and basic research, providing a comprehensive overview of the sensory symptoms in PD. © 2016 Wiley Periodicals, Inc.
Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by an expanded CAG repeat within the huntingtin (HTT) gene. The Q140 and HdhQ150 knock-in HD mouse models were generated such that HdhQ150 mice have an expanded CAG repeat inserted into the mouse Htt gene, whereas in the Q140s, mouse exon 1 Htt was replaced with a mutated version of human exon 1. By standardizing mouse strain background, breeding to homozygosity and employing sensitive behavioral tests, we demonstrate that the onset of behavioral phenotypes occurs earlier in the Q140 than the HdhQ150 knock-in mouse models and that huntingtin (HTT) aggregation appears earlier in the striata of Q140 mice. We have previously found that the incomplete splicing of mutant HTT from exon 1 to exon 2 results in the production of a small polyadenylated transcript that encodes the highly pathogenic mutant HTT exon 1 protein. In this report, we have identified a functional consequence of the sequence differences between these two models at the RNA level, in that the level of incomplete splicing, and of the mutant exon 1 HTT protein, are greater in the brains of Q140 mice. While differences in the human and mouse exon 1 HTT proteins (e.g., proline rich sequences) could also contribute to the phenotypic differences, our data indicate that the incomplete splicing of HTT and approaches to lower the levels of the exon 1 HTT transcript should be pursued as therapeutic targets.
A wealth of research over the past 2 decades has expanded our understanding of the impact of early-life adversity on physiological function and, consequently, health and wellbeing in later life. Early-life adversity increases the risk of developing a number of disorders, such as chronic pain, fibromyalgia, and irritable bowel syndrome. Although much of the research has examined the impact of physical maltreatment, an increasing number of studies have been published over the past few years examining the effect of childhood psychological stress and trauma on the development of various types of chronic pain conditions. We review the clinical and preclinical data examining the link among early-life psychological stress, altered nociceptive behavior, and chronic pain in later life. Evidence supporting a role for certain key neurobiological substrates, including the hypothalamic-pituitary-adrenal axis; monoaminergic, opioidergic, endocannabinoid and immune systems; and epigenetic mechanisms in the association between early-life psychological stress and chronic pain, is provided. Greater understanding of the impact of early-life stress may inform the development of personalized treatments for chronic pain in later life and strategies to prevent its onset in susceptible individuals. © 2016 Wiley Periodicals, Inc.
Sex differences in behavior and developmental trajectories in human children are of great interest to researchers in a variety of fields, and a persistent topic of discussion and debate is the relative contribution of biological vs. social influences to such differences. Given the potentially large effects of cultural and social influences on human child development, nonhuman primates are important model species for investigating the biological and evolutionary roots of sex differences in human development. This Mini-Review briefly summarizes the existing literature on sex-biased behavior toward infant nonhuman primates by mothers and other social partners, followed by a review of findings on sex differences (or lack thereof) in primate behavioral development from a variety of species in wild and naturalistic settings. These include differences in physical and social development, including play, grooming, and object manipulation patterns, as well as nursing and the development of foraging behavior. The Mini-Review concludes by providing potential avenues for future research. © 2016 Wiley Periodicals, Inc.
Melatonin is a neurohormone secreted from the pineal gland and has a wide-ranging regulatory and neuroprotective role. It has been reported that melatonin level is disturbed in some neurological conditions such as stroke, Alzheimer’s disease, and Parkinson’s disease, which indicates its involvement in the pathophysiology of these diseases. Its properties qualify it to be a promising potential therapeutic neuroprotective agent, with no side effects, for some neurological disorders. This review discusses and localizes the effect of melatonin in the pathophysiology of some diseases.
The difference between male and female behavior and male and female susceptibility to a number of neuropsychiatric conditions is not controversial. From a biological perspective, one might expect to see at least some of these differences underpinned by identifiable physical differences in the brain. This Mini-Review focuses on evidence that plasticity mechanisms differ between males and females and ask at what scale of organization the differences might exist, at the systems level, the circuits level, or the synaptic level. Emerging evidence suggests that plasticity differences may extend to the scale of synaptic mechanisms. In particular, the CaMKK, NOS1 and estrogen receptor pathways show sexual dimorphisms with implications for plasticity in the hippocampus and cerebral cortex. © 2016 The Authors. Journal of Neuroscience Research Published by Wiley Periodicals, Inc.
No study investigated whether the presence of specific medical comorbidities is associated with the type of traumatic event, in particular with terrorist attack (TA). In a group of subjects with posttraumatic stress disorder (PTSD), the current study investigated the association between the types of traumatic event (TA vs. other traumatic event [OTE]) and medical comorbidities, controlling for sex and PTSD duration. The Mini International Neuropsychiatric Interview, the Clinician-Administered PTSD Scale, and the Davidson Trauma Scale were administered to 84 subjects diagnosed with PTSD. Thirty-nine were victims of TA and 45 victims of OTE. TA was associated with higher prevalence of neoplasms (β = 2.60, p = 0.02). Females were more protected than males from circulatory system comorbidities (β = 1.47, p = 0.04), while PTSD duration was associated with higher prevalence of such comorbidities (β = 0.005, p = 0.01). Females showed a higher prevalence of neoplasms than males (β = 2.50, p = 0.02). Female sex was protective against metabolic syndrome (β = -1.79, p = 0.02). Patients with PTSD due to TA and female patients should be considered for their higher prevalence of neoplasms, while male patients and those with higher symptom duration should be monitored for circulatory disease and metabolic syndrome. Symptom duration might be associated with circulatory and metabolic disease. Implications for tailored and timely psychopharmacological and psychotherapeutic intervention for PTSD are discussed focusing on these specific medical comorbidities.
Parallel corticostriatonigral circuits have been proposed that separately process motor, cognitive, and emotional-motivational information. Functional integration requires that interactions exist between neurons participating in these circuits. This makes it imperative to study the complex anatomical substrate underlying corticostriatonigral circuits. It has previously been proposed that dopaminergic neurons in the ventral mesencephalon may play a role in this circuit interaction. Therefore, we studied in rats convergence of basal ganglia circuits by depositing an anterograde neuroanatomical tracer into the ventral striatum together with a retrograde fluorescent tracer ipsilaterally in the dorsolateral striatum. In the mesencephalon, using confocal microscopy, we looked for possible appositions of anterogradely labeled fibers and retrogradely labeled neurons, “enhancing” the latter via intracellular injection of Lucifer Yellow. Tyrosine hydroxylase (TH) immunofluorescence served to identify dopaminergic neurons. In neurophysiological experiments, we combined orthodromic stimulation in the medial ventral striatum with recording from ventral mesencephalic neurons characterized by antidromic stimulation from the dorsal striatum. We observed terminal fields of anterogradely labeled fibers that overlap populations of retrogradely labeled nigrostriatal cell bodies in the substantia nigra pars compacta and lateral ventral tegmental area (VTA), with numerous close appositions between boutons of anterogradely labeled fibers and nigrostriatal, TH-immunopositive neurons. Neurophysiological stimulation in the medial ventral striatum caused inhibition of dopaminergic nigrostriatal neurons projecting to the ventrolateral striatal territory. Responding nigrostriatal neurons were located in the medial substantia nigra and adjacent VTA. Our results strongly suggest a functional link between ventromedial, emotional-motivational striatum, and the sensorimotor dorsal striatum via dopaminergic nigrostriatal neurons.