Neurogenesis in the dentate gyrus of the rat following electroconvulsive shock seizures

Electroconvulsive shock (ECS) seizures provide an animal model of electroconvulsive therapy (ECT) in humans. Recent evidence indicates that repeated ECS seizures can induce long-term structural and functional changes in the brain, similar to those found in other seizure models. We have examined the effects of ECS on neurogenesis in the dentate gyrus of the adult rat using bromodeoxyuridine (BrdU) immunohistochemistry, which identifies newly generated cells. Cells have also been labeled for neuronal nuclear protein (NeuN) to identify neurons. One month following eight ECS seizures, ECS-treated rats had approximately twice as many BrdU-positive cells as sham-treated controls. Eighty-eight percent of newly generated cells colabeled with NeuN in ECS-treated subjects, compared to 83% in sham-treated controls. These data suggest that there is a net increase in neurogenesis within the hippocampal dentate gyrus following ECS treatment. Similar increases have been reported following kindling and kainic acid- or pilocarpine-induced status epilepticus. Increased neurogenesis appears to be a general response to seizure activity and may play a role in the therapeutic effects of ECT.     

Electroconvulsive seizures induce proliferation of NG2-expressing glial cells in adult rat amygdala.

BACKGROUND: Volumetric changes and glial pathology have been reported in the amygdala in patients with major depressive disorder. Here we report an analysis of glial cell proliferation in response to electroconvulsive seizures (ECS), clinically used for the treatment of severe depression. METHODS: Male Wistar rats were subjected to five ECS-treatments and then injected with bromodeoxyuridine (BrdU) to detect cell proliferation in the amygdala. The animals were transcardially perfused either 12 hours or 3 weeks after the last BrdU injection. Tissue sections were double-stained for BrdU and the cell-type markers NG2, OX-42, RIP, S-100beta, Doublecortin, or NeuN. RESULTS: Electroconvulsive seizures dramatically increased the proliferation of amygdala cells expressing the oligodendrocyte progenitor marker NG2. Bromodeoxyuridine-labeled NG2-expressing cells were still present after 3 weeks of survival, and a small proportion of the proliferating cells had differentiated into mature oligodendrocytes. CONCLUSIONS: Major depression has been associated with a reduction of glial cells. Our results show that ECS, an antidepressant treatment, significantly increases the number of NG2+ glial cells and mature oligodendrocytes in the adult rat amygdala.     

Corticosterone-induced inhibition of gliogenesis in rat hippocampus is counteracted by electroconvulsive seizures.

BACKGROUND: Volumetric changes and glial pathology have been reported in the central nervous system (CNS) of patients with depressive disorder, an illness often associated with elevated glucocorticoid levels. Glucocorticoids reduce gliogenesis in the adult rat CNS. Electroconvulsive seizure (ECS)-treatment, an animal model for the antidepressant treatment electroconvulsive therapy, can enhance proliferation of glial cells. This study examined glial cell proliferation in response to ECS in rats whose glucocorticoid levels were elevated to mimic the conditions seen in depression. METHODS: Rats were injected daily for seven days with either corticosterone or vehicle. ECS- or sham- treatment was given once daily during the first five days. Proliferating cells in the hippocampus were labeled with bromodeoxyuridine and analyzed for co-labeling with the glial cell markers NG2, Ox42, S-100beta and Rip. RESULTS: ECS counteracted the glucocorticoid-induced inhibition of NG2+, Ox42+ and Rip+ cell proliferation, and the gliogenesis rate was restored to baseline levels. Volumetric changes in rats treated with ECS were detected. CONCLUSIONS: Our results show that ECS-treatment affects the proliferation of glial cells even in the presence of elevated levels of glucocorticoids. This result adds to an increasing number of studies suggesting that antidepressant treatment can counteract degenerative processes associated with major depression.     

Genetic fate mapping of type‐1 stem cell‐dependent increase in newborn hippocampal neurons after electroconvulsive seizures

Electroconvulsive therapy (ECT) is a uniquely effective treatment for major depressive disorder. An increase in hippocampal neurogenesis is implicated in the recovery from depression. We used an inducible genetic mouse model in which only GFAP‐expressing stem‐like cells (type‐1 cells) and their progeny are selectively labeled with the reporter protein β‐galactosidase to track the process of neurogenesis in the dentate gyrus over 3 months following electroconvulsive seizures (ECS), the mouse equivalent of ECT. All ECS protocols tested induced a transient increase in type‐1 cell divisions. While this led to an expansion of the type‐1 cell pool after high‐frequency ECS sessions for 5 consecutive days (5‐ECS), asymmetric divisions drove neurogenesis by giving rise to Doublecortin (DCX)‐expressing neuroblasts that matured into NeuN+ neurons. Significantly, the increase in newly generated DCX+ and NeuN+ cells after 5‐ECS could be traced back to proliferating type‐1 cells. Low‐frequency continuation ECS (c‐ECS) consisting of five single ECS sessions administered every 2 weeks resulted in a similar increase in newborn neurons as the high‐frequency 5‐ECS protocol. Moreover, the combination of 5‐ECS and c‐ECS led to a further significant increase in newborn neurons, suggesting a cellular mechanism responsible for the propitious effects of high‐frequency ECT followed by continuation ECT in severely depressed patients. The ability of high‐ and low‐frequency ECS to induce normally quiescent type‐1 cells to proliferate and generate new neurons sets it apart from other antidepressant treatments and may underlie the superior clinical efficacy of ECT. © 2013 Wiley Periodicals, Inc.     

Electroconvulsive seizures induce proliferation of NG2-expressing glial cells in adult rat hippocampus.

BACKGROUND: Analysis of postmortem tissue from patients with major depression and bipolar disorder has revealed structural changes in several brain regions. We have shown that electroconvulsive seizure (ECS), used for the treatment of severe depression, induces proliferation of both neuronal and nonneuronal cells in the adult rat hippocampus. METHODS: Male Wistar rats were subjected to one or several ECS treatments, then injected with bromodeoxyuridine (BrdU) to detect cell proliferation. Animals were perfused either 1 day or 3 weeks following the last BrdU injection. Cells were double stained for BrdU and the cell type markers chondroitin sulfate proteoglycan (NG2), complement 3-receptor OX-42, 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), Ca(+) binding protein S100-beta, or neuron-specific nuclear protein (NeuN). RESULTS: We identified NG2-expressing cells as a major cell type proliferating in the rat dentate gyrus in response to ECS. A sharp increase in NG2-positive cell proliferation was seen 2 days after ECS, and a large number of NG2-expressing cells persisted at 3 weeks. CONCLUSIONS: Our results show that antidepressant treatment can induce a strong proliferation of glial progenitor cells in the adult rat hippocampus. We propose that this may counteract degenerative changes found in depression and be an important neurobiological event underlying the clinical effect of electroconvulsive seizures.     

Hippocampal neurogenesis is not enhanced by lifelong reduction of glucocorticoid levels

Neurogenesis of dentate gyrus granule cells is generally considered to be negatively regulated by glucocorticoids. We tested the hypothesis that exposure to low plasma corticosteroid levels starting in the early postnatal period enhances granule cell proliferation rate during adulthood. Rat pups were adrenalectomized (ADX) on postnatal day 10 and were then "clamped" throughout life at low corticosterone levels via oral supplementation. Neurogenesis was determined using BrdU immunochemistry at 3 and 12 months in clamped rats as compared with age-matched, sham-operated controls. Rate of neurogenesis did not differ between the groups at either 3 or 12 months. It was significantly lower in 12-month-old compared with 3-month-old rats, despite the presence of an age-dependent increase of plasma corticosterone only in the sham-ADX rats. Granule cell layer volume, granule cell density, and granule cell degeneration (determined using apoptotic markers) were indistinguishable in the two groups, further supporting the comparable rate of neurogenesis under differing chronic glucocorticoid levels. In addition, whereas acute deprivation of plasma glucocorticoids (adrenalectomy) in adult rats evoked a burst of granule cell neurogenesis, complete elimination of these hormones (by stopping hormone supplementation) in adult, early-life ADX/clamped rats did not. These data do not support a simple inverse relationship between chronic plasma glucocorticoid levels and granule cell neurogenesis. Specifically, chronic modulation of glucocorticoid levels commencing early in life evokes additional, adaptive, and compensatory mechanisms that contribute to the regulation of granule cell proliferation.     

帕罗西汀对皮质酮抑制成年大鼠海马细胞增殖的调制作用

目的慢性糖皮质激素治疗叮能导致认知和情感变化,这或许是由于糖皮质激素对海马神经发牛肢细胞增殖的抑制作用造成。帕罗西汀是一种选择性血清素重摄取抑制剂,临床常用作减轻抑郁症状,近几年来发现它能促进海马神经发生。本研究探讨帕罗西汀与慢性糖皮质激素的相耳作用。方法成年大鼠被分成四绀,分别给予芝麻油、皮质酮、帕罗西汀或皮质酮和帕罗西汀十四天。溴脱氧尿嘧啶核苷（5-bromo-2-deoxyuridine,BrdU）免疫组化法被用于定量齿状回的细胞增殖。结果皮质酮抑制了海马的细胞增殖,帕罗西汀增加了海马的细胞增殖。同时给药组还显示帕罗西汀能逆转皮质酮的抑制作用。结论本研究结果对防止海码在类同醇治疗以后的损害或许有临床意义。     

帕罗西汀对皮质酮抑制成年大鼠海马细胞增殖的调制作用(英文)

目的慢性糖皮质激素治疗可能导致认知和情感变化,这或许是由于糖皮质激素对海马神经发生及细胞增殖的抑制作用造成。帕罗西汀是一种选择性血清素重摄取抑制剂,临床常用作减轻抑郁症状,近几年来发现它能促进海马神经发生。本研究探讨帕罗西汀与慢性糖皮质激素的相互作用。方法成年大鼠被分成四组,分别给予芝麻油、皮质酮、帕罗西汀或皮质酮和帕罗西汀十四天。溴脱氧尿嘧啶核苷(5-bromo-2-deoxyuridine,BrdU)免疫组化法被用于定量齿状回的细胞增殖。结果皮质酮抑制了海马的细胞增殖,帕罗西汀增加了海马的细胞增殖。同时给药组还显示帕罗西汀能逆转皮质酮的抑制作用。结论本研究结果对防止海马在类固醇治疗以后的损害或许有临床意义。     

新生期大鼠反复痫性发作的形态学及行为学结果与糖皮质激素水平升高有关(英文)

目的探讨新生期大鼠反复痫性发作后的形态学,行为学以及糖皮质激素水平的变化。方法64只出生后一天的Wistar大鼠随机分为惊厥组40只和对照组24只。惊厥组的新生鼠在出生后1天(P1)、4天(P4)、7天(P7)给予腹腔注射匹罗卡品,制备新生鼠癫痫模型;对照组的新生鼠腹腔注射生理盐水。惊厥组分别在第 3次致痫后在即刻(Ⅰ组)、第4 天(Ⅱ组)、第14 天(Ⅲ组)、第42天(Ⅳ组)四个时间点处死,各时间点设相应对照组,处死前36 h惊厥组和对照组的大鼠腹腔注射BrdU。所有大鼠处死前均取血检测糖皮质激素。第Ⅳ组从P40开始进行Morris水迷宫试验。结果新生鼠3次发作后即刻和第4天与相应日龄对照组相比,齿状回BrdU阳性细胞数明显减少(P<0.05),而癫痫发作后14天和42天BrdU阳性细胞数增加,但发作后14天差异无统计学意义(P>0.05)。在4天的Morris水迷宫试验中,匹罗卡品处理组大鼠到达平台的时间均长于对照组,但是只有第1天和第2天有统计学意义(P<0.05)。检测结果表明高水平的糖皮质激素一直持续到发作后第4天,糖皮质激素水平与BrdU阳性细胞数呈负相关。结论新生大鼠反复痫性发作会造成早期神经发生减少,而后期神经发生增加;造成大鼠成年后认知功能缺陷;造成糖皮质激素水平增高,这与痫性大鼠形态学和行为学方面的改变有关。     

新生期大鼠反复痫性发作的形态学及行为学结果与糖皮质激素水平升高有关

目的探讨新生期大鼠反复痫性发作后的形态学,行为学以及糖皮质激素水平的变化。方法64只出生后一天的Wistar大鼠随机分为惊厥组40只和对照组24只。惊厥组的新生鼠在出生后1天（P1）、4天（P4）、7天（P7）给予腹腔注射匹罗卡品,制备新生鼠癫痫模型;对照组的新生鼠腹腔注射生理盐水。惊厥组分别在第3次致痫后在即刻（Ⅰ组）、第4天（Ⅱ组）、第14天（Ⅲ组）、第42天（Ⅳ组）四个时间点处死,各时间点设相应对照组,处死前36h惊厥组和对照组的大鼠腹腔注射BrdU。所有大鼠处死前均取血检测糖皮质激素。第Ⅳ组从P40开始进行Morris水迷宫试验。结果新生鼠3次发作后即刻和第4天与相应日龄对照组相比,齿状回BrdU阳性细胞数明显减少（P〈0．05）,而癫痫发作后14天和42天BrdU阳性细胞数增加,但发作后14天差异无统计学意义（P〉0．05）。在4天的Morris水迷宫试验中,匹罗卡品处理组大鼠到达平台的时间均长于对照组,但是只有第1天和第2天有统计学意义（P〈0．05）。检测结果表明高水平的糖皮质激素一直持续到发作后第4天,糖皮质激素水平与BrdU阳性细胞数呈负相关。结论新生大鼠反复痫性发作会造成早期神经发生减少,而后期神经发生增加;造成大鼠成年后认知功能缺陷;造成糖皮质激素水平增高,这与痫性大鼠形态学和行为学方面的改变有关。     

Increased neurogenesis and the ectopic granule cells after intrahippocampal BDNF infusion in adult rats

There is evidence that BDNF influences the birth of granule cells in the dentate gyrus, which is one of the few areas of the brain that demonstrates neurogenesis throughout life. However, studies to date have not examined this issue directly. To do so, we compared the effects of BDNF, phosphate-buffered saline (PBS), or bovine serum albumin (BSA) on neurogenesis after infusion into the hippocampus of the normal adult rat, using osmotic pumps that were implanted unilaterally in the dorsal hilus. BDNF, PBS, and BSA were infused for 2 weeks. The mitotic marker bromodeoxyuridine (BrdU) was administered twice daily during the 2-week infusion period. At least 1 month after infusion ended, brains were processed immunocytochemically using antibodies to BrdU, a neuronal nuclear protein (NeuN), or calbindin D28K (CaBP), which labels mature granule cells. Stereology was used to quantify BrdU-labeled cells in the dorsal hippocampus that were double-labeled with NeuN or CaBP. There was a statistically significant increase in BrdU(+)/NeuN(+) double-labeled cells in the granule cell layer after BDNF infusion relative to controls. The values for BrdU(+)/NeuN(+) cells were similar to BrdU(+)/CaBP(+) cells, indicating that most new neurons were likely to be granule cells. In addition, BrdU(+)/NeuN(+)-labeled cells developed in the hilar region after BDNF infusion, which have previously only been identified after severe continuous seizures (status epilepticus) and associated pathological changes. Remarkably, neurogenesis was also increased contralaterally, but BDNF did not appear to spread to the opposite hemisphere. Thus, infusion of BDNF to a local area can have widespread effects on hippocampal neurogenesis. The results demonstrate that BDNF administration to the dentate gyrus leads to increased neurogenesis of granule cells. They also show that ectopic granule cells develop after BDNF infusion, which suggests that ectopic migration is not necessarily confined to pathological conditions. These results are discussed in light of the evidence that BDNF increases neuronal activity in hippocampus. Thus, the mechanisms underlying neurogenesis following BDNF infusion could be due to altered activity as well as direct effects of BDNF itself, and this is relevant to studies of other growth factors because many of them have effects on neuronal excitability that are often not considered.     

Kindled seizures enhance young neuron survival in the adult rat dentate gyrus

New neurons continue to be generated throughout adulthood in the dentate gyrus of mammals. This process of neurogenesis is believed to play a role in some forms of learning and memory. Hippocampal-dependent learning tasks have been shown to specifically enhance the survival of new granule neurons. The present study examined the effects of kindled seizures in rats on the survival of young neurons born before the kindling began. Kindled seizures within the perforant path input to the dentate gyrus triggered between 1 and 2 weeks following the injection of bromodeoxyuridine (BrdU), were found to increase the number of BrdU and NeuN co-labeled cells in the granule cell layer by 128% 1 month later. The number of co-labeled cells was not correlated with measures of seizure severity. These results demonstrate that kindled seizures enhance the survival of new born neurons in the adult rat dentate gyrus which may reflect the actions of an activity-dependent mechanism normally involved in hippocampal-dependent learning and memory.     

卡马西平对成年癫大鼠海马齿状回BrdU/NeuN表达水平及其对空间记忆的影响

目的研究卡马西平对成年癫大鼠海马齿状回新生神经元的影响及其与空间记忆之间的关系。方法采用氯化锂和匹罗卡品联合诱导大鼠癫模型,利用5-溴脱氧尿苷嘧啶与神经元核性蛋白双标记观察海马齿状回内源性神经前体细胞分化为成熟神经元的情况;利用行为学分析评价大鼠的空间记忆。结果 (1)卡马西平可增加癫大鼠海马齿状回新生成熟神经元的数量(P<0.05);(2)卡马西平对癫大鼠的空间记忆有明显改善作用(P<0.01)。结论卡马西平增加癫大鼠海马齿状回新生成熟神经元形成,是其改善癫大鼠空间记忆的可能机制之一。     

Increased neurogenesis in a model of electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is a widely used and efficient treatment modality in psychiatry, although the basis for its therapeutic effect is still unknown. Past research has shown seizure activity to be a regulator of neurogenesis in the adult brain. This study examines the effect of a single and multiple electroconvulsive seizures on neurogenesis in the rat dentate gyrus. METHODS: Rats were given either a single or a series of 10 electroconvulsive seizures. At different times after the seizures, a marker of proliferating cells, Bromodeoxyuridine (BrdU), was administered to the animals. Subsequently, newborn cells positive for BrdU were counted in the dentate gyrus. Double staining with a neuron-specific marker indicated that the newborn cells displayed a neuronal phenotype. RESULTS: A single electroconvulsive seizure significantly increased the number of new born cells in the dentate gyrus. These cells survived for at least 3 months. A series of seizures further increased neurogenesis, indicating a dose-dependent mechanism. CONCLUSIONS: We propose that generation of new neurons in the hippocampus may be an important neurobiologic element underlying the clinical effects of electroconvulsive seizures.     

Electroconvulsive stimulation results in long‐term survival of newly generated hippocampal neurons in rats

Electroconvulsive stimulation (ECS) is one of the strongest stimulators of hippocampal neurogenesis in rodents that represents a plausible mechanism for the efficacy of electroconvulsive therapy (ECT) in major depressive disorder. Using design‐based stereological cell counting, we recently documented an initial 2.6‐fold increase in neurogenesis following a clinical relevant schedule of ECS, a treatment also rescuing depression‐like behavior in rats. However, these results gave no demonstration of the longevity of newly generated neurons. The present study is a direct continuation of the previous work aiming to test the hypothesis that rats subjected to ECS in combination with chronic restraint stress (CRS) display increased formation of new hippocampal neurons, which have a potential for long‐term survival. Furthermore, using mediation analysis, we tested if an ECS‐induced increase in neurogenesis facilitates the behavioral outcome of the forced swim test (FST), an animal model of depression. The results showed that ECS in conjunction with CRS stimulates hippocampal neurogenesis, and that a significant quantity of the newly formed hippocampal neurons survives up to 12 months. The new BrdU‐positive neurons showed time‐dependent attrition of ～40% from day 1 to 3 months, with no further decline between 3 and 12 months. ECS did not affect the number of pre‐existing dentate granule neurons or the volume of the dentate granule cell layer, suggesting no damaging effect of the treatment. Finally, we found that, while ECS increases neurogenesis, this formation of new neurons was not associated to ameliorated immobility in the FST. This implies that other ECS‐induced effects than neurogenesis must be part of mediating the antidepressant action of ECS. Taken together, the results of the present study contribute to the basic understanding of the neurogenic effects of ECT, and demonstrate that ECS, neurogenesis and anti‐depressant behavior are not directly linked. © 2016 Wiley Periodicals, Inc.     

Maternal experience inhibits the production of immature neurons in the hippocampus during the postpartum period through elevations in adrenal steroids

Motherhood is accompanied by alterations in numerous nonreproductive behaviors, including learning and memory, as well as anxiety and stress regulation. These functions have been linked to adult neurogenesis in the hippocampus, but the effect of maternal experience on this brain region has not been completely explored. To determine whether the production of new hippocampal granule cells is altered during the postpartum period, we examined the number of proliferating cells and their progeny in the dentate gyrus of primiparous female rats at various time points during the postpartum period while they were caring for their offspring, as well as after weaning. Additionally, we investigated whether cell proliferation in the postpartum female is affected by the presence of offspring and nursing-induced increases in glucocorticoids. Analysis of the number of BrdU-labeled cells revealed that cell proliferation in the dentate gyrus was suppressed in lactating postpartum females until the time of weaning. This effect was temporary; a difference was detectable at 1 week after BrdU-labeling, when the majority of cells expressed a marker of immature and mature granule neurons (TuJ1) but not at 2 weeks, when most cells expressed a marker of mature neurons (NeuN). The decrease in cell proliferation was dependent on elevated basal glucocorticoid levels associated with lactation; removal of nursing pups reduced basal corticosterone levels and prevented the decrease in the number of BrdU-labeled cells. Moreover, preventing increased basal corticosterone levels by means of adrenalectomy and low-dose corticosterone replacement eliminated the reduction in cell proliferation. These findings indicate that offspring interactions inhibit adult neurogenesis through changes in adrenal steroids, and further suggest a potential mechanism for alterations in hippocampal function during the postpartum period.     

Spreading depression and focal venous cerebral ischemia enhance cortical neurogenesis

Endogenous neurogenesis can arise from a variety of physiological stimuli including exercise, learning, or "enriched environment" as well as pathological conditions such as ischemia, epilepsy or cortical spreading depression. Whether all these conditions use a common trigger to set off endogenous neurogenesis is yet unclear. We hypothesized that cortical spreading depression(CSD) induces neurogenesis in the cerebral cortex and dentate gyrus after cerebral venous ischemia. Forty-two Wistar rats alternatively underwent sham operation(Sham), induction of ten CSDs or venous ischemia provoked via occlusion of two adjacent superficial cortical vein followed by ten induced CSDs(CSD + 2-VO). As an additional control, 15 na?ve rats received no intervention except 5-bromo-2′-deoxyuridine(Brd U) treatment for 7 days. Sagittal brain slices(40 μm thick) were co-stained for Brd U and doublecortin(DCX; new immature neuronal cells) on day 9 or Neu N(new mature neuronal cells) on day 28. On day 9 after sham operation, cell proliferation and neurogenesis occurred in the cortex in rats. The sole induction of CSD had no effect. But on days 9 and 28, more proliferating cells and newly formed neurons in the ipsilateral cortex were observed in rats subjected to CSD + 2VO than in rats subjected to sham operation. On days 9 and 28, cell proliferation and neurogenesis in the ipsilateral dentate gyrus was increased in sham-operated rats than in na?ve rats. Our data supports the hypothesis that induced cortical neurogenesis after CSD + 2-VO is a direct effect of ischemia, rather than of CSD alone.     

Transient calretinin expression defines early postmitotic step of neuronal differentiation in adult hippocampal neurogenesis of mice

We here show that the early postmitotic stage of granule cell development during adult hippocampal neurogenesis is characterized by the transient expression of calretinin (CR). CR expression was detected as early as 1 day after labeling dividing cells with bromodeoxyuridine (BrdU), but not before. Staining for Ki-67 confirmed that no CR-expressing cells were in cell cycle. Early after BrdU, CR colocalized with immature neuronal marker doublecortin; and later with persisting neuronal marker NeuN. BrdU/CR-labeled cells were negative for GABA and GABAA1 receptor, but early on expressed granule cell marker Prox-1. After 6 weeks, no new neurons expressed CR, but all contained calbindin. Stimuli inducing adult neurogenesis have limited (enriched environment), strong (voluntary wheel running), and very strong effects on cell proliferation (kainate-induced seizures). In these models the induction of cell proliferation was paralleled by an increase of CR-positive cells, indicating the stimulus-dependent progression from cell division to a postmitotic stage.     

Quantitative hippocampal structural changes following electroconvulsive seizure treatment in a rat model of depression

Objective: The pathophysiology of depression and the effects of antidepressant treatment are hypothesized to be related to hippocampal structural changes. This study aims to investigate the effect of electroconvulsive seizures on behavior and hippocampal structure in a rat model of depression. Methods: Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats were treated daily for 10 days with either electroconvulsive seizures or sham treatment. The behavior was evaluated using the forced swim test. Design‐based stereological methods were used to quantify the hippocampal volume and the numbers of neurons and glial cells in specific hippocampal subregions. Results: The basal level of hippocampal volume and neuron number differed significantly between the two rat strains, and a trend toward the FSL strain having more glial cells was found. The structural differences found between the sham‐treated animals were counteracted by electroconvulsive seizure (ECS) treatment, which also normalized the behavior. ECS treatment increased the number of glial cells in hilus significantly in the FRL rats and with the same tendency for the FSL rats. Conclusion: Our results indicate that along with hippocampal neurogenesis, gliogenesis may also be involved in the pathophysiology of depression and in the effect of antidepressant treatment. The underlying mechanisms remain unknown, and further investigations are required to clarify whether the structural changes are necessary to induce a therapeutic effect of antidepressant treatment or if they rather represent an epiphenomenon. Synapse, 2012. © 2012 Wiley Periodicals, Inc.     

Neurogenesis and neuroapoptosis in different brain structures of adult Wistar rats

In our study, which was performed with adult Wistar rats, we investigated the pecularities of neurogenesis in different brain regions known for their association with learning and memory. The number of cells positively stained for BrdU (marker of cellular proliferation) was counted at 24 hours, 15 days, and 30 days after BrdU administration in the dentate gyrus, CA1-CA4 hippocampal subfields, different areas of the cerebral cortex, and the cerebellar vermis using the immunofluorescence method. In these brain structures, we also counted the number of new cells that were double stained for neuronal (NeuN), astrocytic (GAFP), or apoptotic (ApoDNA) markers at all examined time points. It was found that in all the studied brain regions, new cells were generated and these cells further differentiated in the neurons and astrocytes. Significant inter-structure differences were found in the proliferation, differentiation, and apoptotic death of newly generated cells. The possible reasons for inconsistencies between our data on neurogenesis/apoptosis and those obtained by other researchers in adult Wistar rats are discussed.