Life and death in the hippocampus: What's bad? Santos, Victor Rodrigues; Melo, Igor santana; Pacheco, Amanda Larissa Dias ...
Epilepsy & behavior,
August 2021, 2021-08-00, 20210801, Letnik:
121
Journal Article
Recenzirano
The hippocampal formation is crucial for the generation and regulation of several brain functions, including memory and learning processes; however, it is vulnerable to neurological disorders, such ...as epilepsy. Temporal lobe epilepsy (TLE), the most common type of epilepsy, changes the hippocampal circuitry and excitability, under the contribution of both neuronal degeneration and abnormal neurogenesis. Classically, neurodegeneration affects sensitive areas of the hippocampus, such as dentate gyrus (DG) hilus, as well as specific fields of the Ammon's horn, CA3, and CA1. In addition, the proliferation, migration, and abnormal integration of newly generated hippocampal granular cells (GCs) into the brain characterize TLE neurogenesis. Robust studies over the years have intensely discussed the effects of death and life in the hippocampus, though there are still questions to be answered about their possible benefits and risks. Here, we review the impacts of death and life in the hippocampus, discussing its influence on TLE, providing new perspectives or insights for the implementation of new possible therapeutic targets.
This article is part of the Special Issue “NEWroscience 2018”.
•Selective degeneration in hippocampus is a consequence of TLE.•Hilar interneurons and pyramidal neurons may degenerate in TLE.•Neuronal death is temporal- and spatial-dependent in hippocampus after TLE.•Newborn neurons are involved in TLE modulation.•Abnormal integrations emerge in newly generated granule cells.
Abuse-related drug usage is a public health issue. Drosophila melanogaster has been used as an animal model to study the biological effects of these psychoactive substances in preclinical studies. ...Our objective in this review is to evaluate the adverse effects produced by cocaine, nicotine, and marijuana during the development of D. melanogaster. We searched experimental studies in which D. melanogaster was exposed to these three psychoactive drugs in seven online databases up to January 2023. Two reviewers independently extracted the data. Fifty-one studies met eligibility criteria and were included in the data extraction: nicotine (n = 26), cocaine (n = 20), and marijuana (n = 5). Fifteen studies were eligible for meta-analysis. Low doses (∼0.6 mM) of nicotine increased locomotor activity in fruit flies, while high doses (≥3 mM) led to a decrease. Similarly, exposure to cocaine increased locomotor activity, resulting in decreased climbing response in D. melanogaster. Studies with exposure to marijuana did not present a profile for our meta-analysis. However, this drug has been less associated with locomotor changes, but alterations in body weight and fat content and changes in cardiac function. Our analyses have shown that fruit flies exposed to drugs of abuse during different developmental stages, such as larvae and adults, exhibit molecular, morphological, behavioral, and survival changes that are dependent on the dosage. These phenotypes resemble the adverse effects of psychoactive substances in clinical medicine.
The cartoon depicts the effects of cocaine, marijuana, and nicotine on the development of Drosophila melanogaster. The articles included in this systematic review indicate that exposure to these drugs of abuse can cause changes at molecular, morphophysiological, and behavioral levels, depending on the dose and route of administration. The chemical structures of the nicotine and cocaine molecules used in this cartoon were taken from the PubChem Compound Summary. National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 89594, Nicotine, and CID 446220, Cocaine. Retrieved August 21, 2023 from https://pubchem.ncbi.nlm.nih.gov/compound/Nicotine and https://pubchem.ncbi.nlm.nih.gov/compound/Cocaine. Display omitted
•Nicotine alters the locomotion of fruit flies in a dose-dependent manner.•Exposure of fruit fly eggs to nicotine increases eclosion by 50%.•Reduced climbing ability in fruit flies after cocaine exposure is sex-dependent.•Repeated cocaine exposure increases locomotor activity in fruit flies.
Temporal lobe epileptic seizures are one of the most common and well-characterized types of epilepsies. The current knowledge on the pathology of temporal lobe epilepsy relies strongly on studies of ...epileptogenesis caused by experimentally induced status epilepticus (SE). Although several temporal lobe structures have been implicated in the epileptogenic process, the hippocampal formation is the temporal lobe structure studied in the greatest amount and detail. However, studies in human patients and animal models of temporal lobe epilepsy indicate that the amygdaloid complex can be also an important seizure generator, and several pathological processes have been shown in the amygdala during epileptogenesis.
Therefore, in the present review, we systematically selected, organized, described, and analyzed the current knowledge on anatomopathological data associated with the amygdaloid complex during SE-induced epileptogenesis. Amygdaloid complex participation in the epileptogenic process is evidenced, among others, by alterations in energy metabolism, circulatory, and fluid regulation, neurotransmission, immediate early genes expression, tissue damage, cell suffering, inflammation, and neuroprotection. We conclude that major efforts should be made in order to include the amygdaloid complex as an important target area for evaluation in future research on SE-induced epileptogenesis.
This article is part of the Special Issue “NEWroscience 2018”.
Display omitted
•Amygdaloid complex participates of Status Epilepticus-induced epileptogenesis in animal models.•A timeline of pathophysiological events in amygdala during epileptogenesis was constructed.•There are evidences of different underlying epileptogenic processes in amygdala as compared to hippocampus.•Amygdala anatomical and functional complexity may cause reduced amount of data collected in epilepsy research.•Stored histopathological material used for epilepsy research on hippocampus may be useful for amygdala evaluation.
Several genetic association investigations have been performed over the last three decades to identify variants underlying Juvenile Myoclonic Epilepsy (JME). Here, we evaluate the accumulating ...findings and provide an updated perspective of these studies.
A systematic literature search was conducted using the PubMed, Embase, Scopus, Lilacs, epiGAD, Google Scholar and Sigle up to February 12, 2016. The quality of the included studies was assessed by a score and classified as low and high quality. Beyond outcome measures, information was extracted on the setting for each study, characteristics of population samples and polymorphisms.
Fifty studies met eligibility criteria and were used for data extraction. With a single exception, all studies used a candidate gene approach, providing data on 229 polymorphisms in or near 55 different genes. Of variants investigating in independent data sets, only rs2029461 SNP in GRM4, rs3743123 in CX36 and rs3918149 in BRD2 showed a significant association with JME in at least two different background populations. The lack of consistent associations might be due to variations in experimental design and/or limitations of the approach.
Thus, despite intense research evidence established, specific genetic variants in JME susceptibility remain inconclusive. We discussed several issues that may compromise the quality of the results, including methodological bias, endophenotype and potential involvement of epigenetic factors.
CRD42016036063.
Status epilepticus (SE) is described as continuous and self-sustaining seizures, which triggers hippocampal neurodegeneration, inflammation, and gliosis.
N
-formyl peptide receptor (FPR) has been ...associated with inflammatory process.
N
-formyl-methionyl-leucyl-phenylalanine (fMLP) peptide plays an anti-inflammatory role, mediated by the activation of G-protein-coupled FPR. Here, we evaluated the influence of fMLP peptides on the behavior of limbic seizures, memory consolidation, and hippocampal neurodegeneration process. Male Wistar rats (
Rattus norvegicus
) received microinjections of pilocarpine in hippocampus (H-PILO, 1.2 mg/μL, 1 μL) followed by fMLP (1 mg/mL, 1 μL) or vehicle (VEH, saline 0.9%, 1 μL). During the 90 min of SE, epileptic seizures were analyzed according to the Racine’s Scale. After 24 h of SE, memory impairment was assessed by the inhibitory avoidance test and the neurodegeneration process was evaluated in hippocampal areas. There was no change in latency and number of wet dog shake (WDS) after administration of fMLP. However, our results showed that the intrahippocampal infusion of fMLP reduced the severity of seizures, as well as the number of limbic seizures. In addition, fMLP infusion protected memory dysfunction followed by SE. Finally, the intrahippocampal administration of fMLP attenuated the process of neurodegeneration in both hippocampi. Taken together, our data suggest a new insight into the functional role of fMLP peptides, with important implications for their potential use as a therapeutic agent for the treatment of brain disorders, such as epilepsy.
Graphical Abstract
Schematic drawing on the neuroprotective and anticonvulsant role of fMLP during status epilepticus. Initially, a cannula was implanted in hippocampus and pilocarpine/saline was administered into the hippocampus followed by fMLP/saline (A-C). fMLP reduced seizure severity and neuronal death in the hippocampus, as well as protecting against memory deficit (D).
Status epilepticus
(SE) can lead to serious neuronal damage and act as an initial trigger for epileptogenic processes that may lead to temporal lobe epilepsy (TLE). Besides promoting ...neurodegeneration, neuroinflammation, and abnormal neurogenesis, SE can generate an extensive hypometabolism in several brain areas and, consequently, reduce intracellular energy supply, such as adenosine triphosphate (ATP) molecules. Although some antiepileptic drugs show efficiency to terminate or reduce epileptic seizures, approximately 30% of TLE patients are refractory to regular antiepileptic drugs (AEDs). Modulation of glucose availability may provide a novel and robust alternative for treating seizures and neuronal damage that occurs during epileptogenesis; however, more detailed information remains unknown, especially under hypo- and hyperglycemic conditions. Here, we review several pathways of glucose metabolism activated during and after SE, as well as the effects of hypo- and hyperglycemia in the generation of self-sustained limbic seizures. Furthermore, this study suggests the control of glucose availability as a potential therapeutic tool for SE.
Objective
Crack cocaine consumption is one of the main public health challenges with a growing number of children intoxicated by crack cocaine during the gestational period. The primary goal is to ...evaluate the accumulating findings and to provide an updated perspective on this field of research.
Methods
Meta-analyses were performed using the random effects model, odds ratio (OR) for categorical variables and mean difference for continuous variables. Statistical heterogeneity was assessed using the
I
-squared statistic and risk of bias was assessed using the Newcastle–Ottawa Quality Assessment Scale. Ten studies met eligibility criteria and were used for data extraction.
Results
The crack cocaine use during pregnancy was associated with significantly higher odds of preterm delivery odds ratio (OR), 2.22; 95% confidence interval (CI), 1.59–3.10, placental displacement (OR, 2.03; 95% CI 1.66–2.48), reduced head circumference (− 1.65 cm; 95% CI − 3.12 to − 0.19), small for gestational age (SGA) (OR, 4.00; 95% CI 1.74–9.18) and low birth weight (LBW) (OR, 2.80; 95% CI 2.39–3.27).
Conclusion
This analysis provides clear evidence that crack cocaine contributes to adverse perinatal outcomes. The exposure of maternal or prenatal crack cocaine is pointedly linked to LBW, preterm delivery, placental displacement and smaller head circumference.
Hypertension is considered one of the most critical risk factors for COVID-19. Evidence suggests that SARS-CoV-2 infection produces intense effects on the cardiovascular system by weakening the wall ...of large vessels via vasa-vasorum. In this commentary, we propose that SARS-CoV-2 invades carotid and aortic baroreceptors, leading to infection of the nucleus tractus solitari (NTS) and paraventricular hypothalamic nucleus (PVN), and such dysregulation of NTS and PVN following infection causes blood pressure alteration at the central level. We additionally explored the hypothesis that SARS-CoV-2 favors the internalization of membrane ACE2 receptors generating an imbalance of the renin-angiotensin-aldosterone system (RAAS), increasing the activity of angiotensin II (ANG-II), disintegrin, and metalloproteinase 17 domain (ADAM17/TACE), eventually modulating the integration of afferents reaching the NTS from baroreceptors and promoting increased blood pressure. These mechanisms are related to the increased sympathetic activity, which leads to transient or permanent hypertension associated with SARS-CoV-2 invasion, contributing to the high number of deaths by cardiovascular implications.
Status epilepticus (SE) is defined as continuous and self-sustaining seizures, which trigger hippocampal neurodegeneration, mitochondrial dysfunction, oxidative stress, and energy failure. During SE, ...the neurons become overexcited, increasing energy consumption. Glucose uptake is increased via the sodium glucose cotransporter 1 (SGLT1) in the hippocampus under epileptic conditions. In addition, modulation of glucose can prevent neuronal damage caused by SE. Here, we evaluated the effect of increased glucose availability in behavior of limbic seizures, memory dysfunction, neurodegeneration process, neuronal activity, and SGLT1 expression. Vehicle (VEH, saline 0.9%, 1 μL) or glucose (GLU; 1, 2 or 3 mM, 1 μL) were administered into hippocampus of male Wistar rats (
Rattus norvegicus
) before or after pilocarpine to induce SE. Behavioral analysis of seizures was performed for 90 min during SE. The memory and learning processes were analyzed by the inhibitory avoidance test. After 24 h of SE, neurodegeneration process, neuronal activity, and SGLT1 expression were evaluated in hippocampal and extrahippocampal regions. Modulation of hippocampal glucose did not protect memory dysfunction followed by SE. Our results showed that the administration of glucose after pilocarpine reduced the severity of seizures, as well as the number of limbic seizures. Similarly, glucose after SE reduced cell death and neuronal activity in hippocampus,
subiculum
, thalamus, amygdala, and cortical areas. Finally, glucose infusion elevated the SGLT1 expression in hippocampus. Taken together our data suggest that possibly the administration of intrahippocampal glucose protects brain in the earlier stage of epileptogenic processes via an important support of SGLT1.
Cyclo-Gly-Pro (CGP) attenuates nociception, however its effects on salivary glands remain unclear. In this study, we investigated the acute effects of CGP on salivary flow and composition, and on the ...submandibular gland composition, compared with morphine. Besides, we characterized the effects of naloxone (a non-selective opioid receptor antagonist) on CGP- and morphine-induced salivary and glandular alterations in mice. After that, in silico analyses were performed to predict the interaction between CGP and opioid receptors. Morphine and CGP significantly reduced salivary flow and total protein concentration of saliva and naloxone restored them to the physiological levels. Morphine and CGP also reduced several infrared vibrational modes (Amide I, 1687-1594cm-1; Amide II, 1594-1494cm-1; CH2/CH3, 1488-1433cm-1; C = O, 1432-1365cm-1; PO2 asymmetric, 1290-1185cm-1; PO2 symmetric, 1135-999cm-1) and naloxone reverted these alterations. The in silico docking analysis demonstrated the interaction of polar contacts between the CGP and opioid receptor Cys219 residue. Altogether, we showed that salivary hypofunction and glandular changes elicited by CGP may occur through opioid receptor suggesting that the blockage of opioid receptors in superior cervical and submandibular ganglions may be a possible strategy to restore salivary secretion while maintaining antinociceptive action due its effects on the central nervous system.
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