Structure Of Hippocampal Neurons Research Articles

Dual-Color 3D Superresolution Microscopy by Combined Spectral-Demixing and Biplane Imaging

Multicolor three-dimensional (3D) superresolution techniques allow important insight into the relative organization of cellular structures. While a number of innovative solutions have emerged, multicolor 3D techniques still face significant technical challenges. In this Letter we provide a straightforward approach to single-molecule localization microscopy imaging in three dimensions and two colors. We combine biplane imaging and spectral-demixing, which eliminates a number of problems, including color cross-talk, chromatic aberration effects, and problems with color registration. We present 3D dual-color images of nanoscopic structures in hippocampal neurons with a 3D compound resolution routinely achieved only in a single color.

Mitochondrial Toxic Effects of Aβ Through Mitofusins in the Early Pathogenesis of Alzheimer’s Disease

Mitochondrial dysfunction has been implicated in the pathogenesis of Alzheimer's disease (AD). However, it is obscure how amyloid-beta (Aβ) can impair mitochondria in the early stage of AD pathology. Using PrP-hAPP/hPS1 double-transgenic AD mouse model, we find that abnormal mitochondrial morphology and damaged mitochondrial structure in hippocampal neurons appear in the early stage of AD-like disease development. We also find consistent mitochondrial abnormalities in the SH-SY5Y cells, which express amyloid precursor protein (APP) Swedish mutation (APPsw) and have been used as a cell model of the early-onset AD. Significant changes of mitofusin GTPases (Mfn1 and Mfn2) were detected both in the PrP-hAPP/hPS1 brains and SH-SY5Y cells. Moreover, our results show that Aβ accumulation in neurons of PrP-hAPP/hPS1 mice can affect the neurogenesis prior to plaque formation. These findings suggest that mitochondrial impairment is a very early event in AD pathogenesis and abnormal expression of Mfn1 and Mfn2 caused by excessive intracellular Aβ is the possible molecular mechanism. Interestingly, L-theanine has significant effects on regulating mitochondrial fusion proteins in SH-SY5Y (APPsw) cells. Overall, our results not only suggest a new early mechanism of AD pathogenesis but also propose a preventive candidate, L-theanine, for the treatment of AD.

Effects of propofol on intracellular calcium ion concentration and NF-κB activity in hippocampal neurons of fetal rats in vitro

Objective To evaluate the effects of propofol on the intracellular calcium ion concentration （[Ca2＋ ]i） and nuclear factor kappa B （NF-κB） activity in hippocampal neurons of fetal rats in vitro .Methods Ten pregnant Sprague-Dawley rats at 16-18 days of gestation ,were sacrificed and the fetal rats were taken out from the abdominal cavity .The hippocampal neurons of the fetal rats were isolated and seeded in culture plates .After being cultured for 9 days ,the neurons were divided into 7 groups （ n=12 each ） using a random number table ：control group （C group） ,intralipid group （I group） and propofol 0.1 ,1 ,10 ,100 ,1 000 μmol/L groups （P1-5 groups） .In group I ,10% intralipid was added to the culture media until the final concentration reached 100μmol/L .In P1-5 groups ,propofol was added to the culture media until the final concentration reached 0.1 ,1 ,10 , 100 and 1 000μmol/L ,respectively .The cells were then incubated for 3 h .The [Ca2＋ ]i and cellular morphology of hippocampal neurons were examined by laser scanning confocal microscopy before incubation with propofol and within 10 min after the end of incubation with propofol .The expression of NF-κB protein in the nucleus was＆nbsp;detected at 7 days after the end of incubation with propofol by Western blot analysis to reflect NF-κB activity . Results Propofol increased [Ca2＋ ]i in P2-4 groups ,while decreased [Ca2＋ ]i in group P5 （ P0.05 ） .The structure of hippocampal neurons was normal in C ,I and P1 groups .The branchings of axons and dendrites in hippocampal neurons were significantly decreased in P 2-4 groups , while the structure of hippocampal neurons became fuzzy , the cell membrane was destroyed and the axons and dendrites were not seen in group P5 .Conclusion Propofol can produce neurotoxic effects on hippocampal neurons of fetal rats by changing the [Ca2＋ ]i and promoting NF-κB activation in vitro . Key words: Propofol; Fetus; Hippocampus; Neurons; Calcium; NF-kappa B

Chronic Alcohol Alters Dendritic Spine Development in Neurons in Primary Culture

Dendritic spines are specialised membrane protrusions of neuronal dendrites that receive the majority of excitatory synaptic inputs. Abnormal changes in their density, size and morphology have been associated with various neurological and psychiatric disorders, including those deriving from drug addiction. Dendritic spine formation, morphology and synaptic functions are governed by the actin cytoskeleton. Previous in vivo studies have shown that ethanol alters the number and morphology of spines, although the mechanisms underlying these alterations remain unknown. It has also been described how chronic ethanol exposure affects the levels, assembly and cellular organisation of the actin cytoskeleton in hippocampal neurons in primary culture. Therefore, we hypothesised that the ethanol-induced alterations in the number and shape of dendritic spines are due to alterations in the mechanisms regulating actin cytoskeleton integrity. The results presented herein show that chronic exposure to moderate levels of alcohol (30mM) during the first 2weeks of culture reduces dendritic spine density and alters the proportion of the different morphologies of these structures in hippocampal neurons, which affects the formation of mature spines. Apparently, these effects are associated with an increase in the G-actin/F-actin ratio due to a reduction of the F-actin fraction, leading to changes in the levels of the different factors regulating the organisation of this cytoskeletal component. The data presented herein indicate that these effects occur between weeks 1 and 2 of culture, an important period in dendritic spines development. These changes may be related to the dysfunction in the memory and learning processes present in children prenatally exposed to ethanol.

Characterization and distribution of adaptor protein containing a PH domain, PTB domain and leucine zipper motif (APPL1) in Alzheimer’s disease hippocampus: an immunohistochemical study

Adaptor protein containing a PH domain, PTB domain and leucine zipper motif (APPL1) is emerging as a critical regulator of various cellular processes in non-neuronal cells as well as in neurons where it localizes to dendritic spines and synapses. It regulates the development of these structures in hippocampal neurons. Although memory impairment in Alzheimer’s disease (AD) has been attributed to disruption of synaptic plasticity, there is scant information on this protein in the human brain. In the present study, we immunohistochemically characterized the localization of APPL1 in AD and control brains. APPL1 accumulated perisomatically as granules around neurons within vulnerable sectors of the hippocampus (CA1 and subiculum) in AD brain, whilst APPL1-positive granules were rarely identified in control brains derived from elderly individuals with no known cognitive impairment. Interestingly, in the AD hippocampus, APPL1 also co-localized with perisomatic granules (non-plaque dystrophic dendrites) expressing glutamate receptor 2 and ubiquitin, suggesting the possible involvement of APPL1 in the synaptic modifications in AD. Thus, the immunohistochemical distribution of APPL1 in AD brain was distinct from that in non-AD control brains, suggesting that signaling via APPL1 might play a critical role in the memory impairment in AD.

Changes in the synaptic structure of hippocampal neurons and impairment of spatial memory in a rat model caused by chronic arsenite exposure

Many epidemiological studies and in vitro experiments have found that chronic arsenic exposure may influence memory formation. The goal of this study was to create an animal model of memory impairment induced by chronic arsenite exposure and to study the underlying mechanisms. Sixty male Sprague-Dawley (SD) male rats were randomly divided into a control group, a low-dose sodium arsenite exposure group and a high-dose sodium arsenite exposure group. Sodium arsenite was administered by adding it to drinking water for 3 months. Then, the spatial memory of the rats was examined with Morris water maze and Y maze. The concentration of arsenic in the blood and the brain was determined by an atomic fluorescence absorption spectrometer. The ultra-structure of hippocampal neurons was observed by an electron microscope. Timm staining was used for observing mossy fibers. We found that the concentration of arsenic in the blood and the brain increased in a dose–response manner (P<0.05). The performance of rats in the arsenite exposed group (15mg/kg) was significantly impaired in the Morris water maze and Y maze tasks than those in the control group (P<0.05). Sodium arsenite exposure resulted in abnormal structural changes in the myelin sheaths of nerve fibers and decreases in the terminals of mossy fibers. Together, chronic sodium arsenite exposure through drinking water results in detrimental changes in the neuronal synapses, which may contribute to the arsenite-induced impairment of spatial memory.

Effects of propofol on expression of hippocampal survivin and Caspase-3 in newborn rats

Intravenous anesthetics, such as propofol, are widely used in general anesthesia. Neurodegeneration and neurocognitive impairment after exposure to propofol in neonatal rats have raised concerns regarding the safety of pediatric anesthesia. We examined the effects of neonatal propofol exposure on brain cell viability, as well as expression of hippocampal survivin and Caspase-3 mRNA and protein. One hundred male Sprague-Dawley rats aged 7 d that were weighed 10-15 g were randomly divided into 4 groups (n = 25 each group). Group A: the rats were injected with no drugs. Group B: the rats were intraperitoneally injected with 50 mg/kg propofol. Group C: the rats were first intraperitoneally injected with 50 mg/kg propofol and another 50 mg/kg propofol was used when the dynamic response of rats appeared again. Group D: the rats were first intraperitoneally injected with 50 mg/kg propofol and another 50 mg/kg propofol was used three times once the dynamic response of rats appeared. To study the effects of propofol exposure on respiratory and metabolic function, arterial blood was aspirated from the left ventricle of neonatal rats 2 h after discontinuation of propofol. pH, PaO(2), PaCO(2), HCO(3)(-), BE and SaO(2) were detected by blood gas analyzer. Moreover, to examine the effects of propofol exposure on short-term cellular viability, the ultrastructure of neurons was observed by transmission electron microscope and Fluoro-Jade B (FJB) staining was performed to examine neuronal degeneration in hippocampal CA1 region of neonatal rats. Survivin and Caspase-3 mRNA and protein expression in hippocampus were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting 2 h after discontinuation of propofol. The time of anesthesia maintaince in newborn rats was the longest in Group D and the time of anesthesia maintaince in Group C was longer than that in Group B. Two hours after discontinuation of propofol, pH, PaO(2), PaCO(2), HCO(3)(-), BE and SaO(2) of arterial blood in rats were not significantly different among groups A, B, C and D (P > 0.05). The structure of hippocampal neurons was normal in Group A and Group B while 100 mg/kg propofol resulted in nuclear blebbing and 200 mg/kg propofol led to nuclear fragmentation, chromatin condensation and apoptotic bodies. Cellular degeneration, as measured by Fluoro-Jade B staining, significantly increased in hippocampal CA1 region in the anesthesia groups compared with littermates in the no anesthesia group. FJB-positive stained degenerative neurons in groups B, C and D were (2.5 ± 1.3), (7.1 ± 2.3) and (9.4 ± 2.6), which were different from that in Group A (0.6 ± 0.3) (P < 0.05). Moreover, the number of FJB-positive neurons was the highest in Group D, that in Group C was more than that in Group B. At the same time point, apoptosis was measured by expression of Caspase-3 and Survivin mRNA and protein in hippocampus of rats. Caspase-3 mRNA in groups A, B and C was (0.78 ± 0.12), (0.84 ± 0.17) and (0.89 ± 0.19), while Caspase-3 protein in groups A, B and C was (0.22 ± 0.05), (0.26 ± 0.07) and (0.21 ± 0.06). Survivin mRNA in groups A, B and C was (0.56 ± 0.12), (0.58 ± 0.15) and (0.53 ± 0.16), while Survivin protein in these 3 groups was (0.24 ± 0.07), (0.21 ± 0.05) and (0.23 ± 0.06). Compared with that in Group A, Caspase-3 and Survivin mRNA and protein were not significantly different among Group B and Group C (P > 0.05). However, Caspase-3 mRNA and protein in Group D were (1.21 ± 0.14) and (0.42 ± 0.12), which were higher than that in the other 3 groups (P < 0.05). Survivin mRNA and protein in Group D were lower than that in the other 3 groups (P < 0.05). A high dose of propofol exposure may destroy the structure of neurons, induce neurodegeneration, increase Caspase-3 activity and inhibit survivin expression in hippocampus of newborn rats in vivo.

The relation of learning deficits with oxidative stress in rats exposed to severe intermittent hypoxia

To observe the relations between learning memory function and oxidative stress in rats exposed to severe intermittent hypoxia (IH). Adult male Wistar rats (n = 48) were randomly assigned to 2 groups: untreated control group (UC) and 5% intermittent hypoxia group (5%IH). At 2, 4, 6 and 8 weeks, the learning and memory ability of the rats in each group were assessed with the Morris water maze (MWM) test. The ultrastructural changes in the hippocampus of the rats were observed with transmission electron microscopy (TEM). The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were detected by colorimetric method. The water maze test showed that the rats in the 5% IH group had prolonged latency in escaping, reduced target quadrant time in crossing and reduced frequency of crossing the platform, as compared to the UC group (P < 0.05). With longer time of hypoxia, the damage became more significant. It was observed that the structure of neuron cell was complete and organelles were abundant in UC groups. With the extension of exposure time, the number of hippocampus neurons and synaptic were decreased in 5%IH groups, nucleus shrank, synaptic frame became indefinite and synaptic cleft widen. Comparing with control group, the level of MDA in the hippocampal region group was significantly higher (P < 0.05) and the activity of SOD significantly was lower (P < 0.05) in 5%IH, along with the time expand, which aggravated. Severe intermittent hypoxia that results in learning and memory dysfunction. It is possible that oxidative stress change the quantity and structure of hippocampal neurons and synaptic, which aggravates along with the intermittent low oxygen time expand.

Effect of β‐amyloid (25–35) on mitochondrial function and expression of mitochondrial permeability transition pore proteins in rat hippocampal neurons

The aim of this study was to assess the effect of the β-amyloid fragment Aβ(25-35) on mitochondrial structure and function and on the expression of proteins associated with the mitochondrial permeability transition pore (MPTP) in rat hippocampal neurons. Ninety clean-grade Sprague-Dawley rats were randomly assigned to six groups (n = 15 per group). Aβ(25-35) (1, 5, or 10 µg/rat) was injected into hippocampal area CA1. Normal saline was injected as a control. The effect of Aβ(25-35) injection on hippocampal structure was assessed by transmission electron microscopy. Ca(2+) -ATPase activity, [Ca(2+) ](i) , and mitochondrial membrane potential were measured. The expression of genes associated with the MPTP, including the voltage-dependent anion channel (VDAC), adenine nucleotide translocator (ANT), and cyclophilin D (Cyp-D), were evaluated. Results showed that Aβ(25-35) injection damaged the mitochondrial structure of hippocampal neurons, decreased Ca(2+) -ATPase activity and mitochondrial membrane potential, and increased [Ca(2+) ](i) . The expression levels for VDAC, ANT, and Cyp-D in all groups were significantly (P < 0.05) higher than those in the normal control group after Aβ(25-35) injection. These results indicate that Aβ(25-35) damages mitochondria in rat hippocampal neurons and effects mitochondrial dysfunction, as well as increasing the expression of genes associated with the MPTP. Mitochondrial dysfunction may result in increased MPTP gene expression, leading to neurodegenerative effects.

Effects of Chinese herbal medicine Yinsiwei compound on spatial learning and memory ability and the ultrastructure of hippocampal neurons in a rat model of sporadic Alzheimer disease

To study the effects of Chinese herbal medicine Yinsiwei compound (YSW) on spatial learning and memory ability in rats with sporadic Alzheimer disease (SAD) and the ultrastructural basis of the hippocampal neurons. A rat model of SAD was established by intracerebroventricular injection of streptozotocin. The rats were divided into six groups: sham-operation group, model group, donepezil control group, and YSW low, medium and high dose groups. Drug interventions were started on the 21st day after modeling and each treatment group was given the corresponding drugs by gavage for two months. Meanwhile, the model group and the sham-operation group were given the same volume of distilled water by gavage once a day for two months. The Morris water maze was adopted to test spatial learning and memory ability of the rats. The place navigation test and the spatial probe test were conducted. The escape latency, total swimming distance and swimming time in the target quadrant of the rats were recorded. Also, the hippocampus tissues of rats were taken out and the ultrastructure of hippocampus neurons were observed by an electron microscope. In the place navigation test, compared with the model group, the mean escape latency and the total swimming distance of the donepezil group and the YSW low, medium and high dose groups were significantly shortened (P<0.05 or P<0.01). In the space probe test, the swimming time of each treatment group in the target quadrant was significantly longer than that of the model group (P<0.05 or P<0.01). For most of the test period, the donepezil group had no significant change compared with the YSW low, medium and high dose groups, respectively. The ultrastructure of the hippocampus neurons under the electron microscope also confirmed the efficacy of the drug treatment. Chinese herbal medicine YSW compound can improve spatial learning and memory impairment of rats with SAD. The ultrastructural basis may be that it can protect the microtubule structures of hippocampal neurons and prevent nerve axons from being damaged.

An APPL1/Akt signaling complex regulates dendritic spine and synapse formation in hippocampal neurons

The formation and plasticity of dendritic spines and synapses, which are poorly understood on a molecular level, are critical for cognitive functions, such as learning and memory. The adaptor protein containing a PH domain, PTB domain, and leucine zipper motif (APPL1) is emerging as a critical regulator of various cellular processes in non-neuronal cells, but its function in the nervous system is not well understood. Here, we show that APPL1 localizes to dendritic spines and synapses and regulates the development of these structures in hippocampal neurons. Knockdown of endogenous APPL1 using siRNA led to a significant decrease in the number of spines as well as synapses and this defect could be rescued by expression of siRNA-resistant APPL1. Expression of exogenous APPL1 increased the spine and synaptic density and the amount of surface GluR1-containing α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs). Deletion of the C-terminal phosphotyrosine binding domain of APPL1, which binds the serine/threonine kinase Akt, resulted in a significant decrease in the spine and synaptic density, suggesting a role for Akt in regulating the development of these structures. Consistent with this, knockdown of Akt with siRNA or expression of dominant negative Akt led to a dramatic decrease in spine and synapse formation. In addition, APPL1 increased the amount of active Akt in spines and synapses and the effects of APPL1 on these structures were dependent on Akt, indicating that Akt is an effector of APPL1 in the regulation of these processes. Moreover, APPL1 signaling modulates spine and synapse formation through p21-activated kinase (PAK). Thus, our results indicate that APPL1 signaling through Akt and PAK is critical for spine and synaptic development and point to a role for APPL1 and its effectors in regulating cognitive function.

Regulation of Synaptic Structure by Ubiquitin C-Terminal Hydrolase L1

Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a deubiquitinating enzyme that is selectively and abundantly expressed in the brain, and its activity is required for normal synaptic function. Here, we show that UCH-L1 functions in maintaining normal synaptic structure in hippocampal neurons. We found that UCH-L1 activity is rapidly upregulated by NMDA receptor activation, which leads to an increase in the levels of free monomeric ubiquitin. Conversely, pharmacological inhibition of UCH-L1 significantly reduces monomeric ubiquitin levels and causes dramatic alterations in synaptic protein distribution and spine morphology. Inhibition of UCH-L1 activity increases spine size while decreasing spine density. Furthermore, there is a concomitant increase in the size of presynaptic and postsynaptic protein clusters. Interestingly, however, ectopic expression of ubiquitin restores normal synaptic structure in UCH-L1-inhibited neurons. These findings point to a significant role of UCH-L1 in synaptic remodeling, most likely by modulating free monomeric ubiquitin levels in an activity-dependent manner.

Protein Kinase D Controls the Integrity of Golgi Apparatus and the Maintenance of Dendritic Arborization in Hippocampal Neurons

Protein kinase D (PKD) is known to participate in various cellular functions, including secretory vesicle fission from the Golgi and plasma membrane-directed transport. Here, we report on expression and function of PKD in hippocampal neurons. Expression of an enhanced green fluorescent protein (EGFP)-tagged PKD activity reporter in mouse embryonal hippocampal neurons revealed high endogenous PKD activity at the Golgi complex and in the dendrites, whereas PKD activity was excluded from the axon in parallel with axonal maturation. Expression of fluorescently tagged wild-type PKD1 and constitutively active PKD1(S738/742E) (caPKD1) in neurons revealed that both proteins were slightly enriched at the trans-Golgi network (TGN) and did not interfere with its thread-like morphology. By contrast, expression of dominant-negative kinase inactive PKD1(K612W) (kdPKD1) led to the disruption of the neuronal Golgi complex, with kdPKD1 strongly localized to the TGN fragments. Similar findings were obtained from transgenic mice with inducible, neuron-specific expression of kdPKD1-EGFP. As a prominent consequence of kdPKD1 expression, the dendritic tree of transfected neurons was reduced, whereas caPKD1 increased dendritic arborization. Our results thus provide direct evidence that PKD activity is selectively involved in the maintenance of dendritic arborization and Golgi structure of hippocampal neurons.

Adolescent development of neuron structure in dentate gyrus granule cells of male syrian hamsters

Hippocampal function, including spatial cognition and stress responses, matures during adolescence. In addition, hippocampal neuron structure is modified by gonadal steroid hormones, which increase dramatically at this time. This study investigated pubertal changes in dendritic complexity of dentate gyrus neurons. Dendrites, spines, and cell bodies of Golgi-impregnated neurons from the granule cell layer were traced in pre-, mid-, and late-pubertal male Syrian hamsters (21, 35, and 49 days of age). Sholl analysis determined the number of intersections and total dendritic length contained in concentric spheres set at 25-microm increments from the soma. Spine densities were quantified separately in proximal and distal segments of a subset of neurons used for the Sholl analysis. We found that the structure of neurons in the lower, but not upper, blade of the dentate gyrus changed during adolescence. The lower, infrapyramidal blade showed pruning of dendrites close to the cell body and increases in distal dendritic spine densities across adolescence. These data demonstrate that dentate gyrus neurons undergo substantial structural remodeling during adolescence and that patterns of maturation are region specific. Furthermore, these changes in dendrite structure, which alter the electrophysiological properties of granule cells, are likely related to the adolescent development of hippocampal-dependent cognitive functions such as learning and memory, as well as hippocampus-mediated stress responsivity.

Growth of Primary Hippocampal Neuronal Tissue on an Aragonite Crystalline Biomatrix

Tissue-like structures of hippocampal neurons were established in a crystalline three-dimensional (3D) aragonite biomatrix obtained from the exoskeleton of the coral Porites lutea. Cultures were maintained in vitro for up to 5 weeks. Cell viability and regeneration of neuronal properties were studied by immunocytochemical methods, light microscopy image analysis techniques, and scanning electron microscopy. Some portions of the cell population acquired the morphological characteristics of hippocampal pyramidal or granule neurons with axons and dendrites extending in a 3D manner along the surfaces of the crystalline biomatrix. The neurons usually grew on a sheet of glial cells. Within the pore void areas, multiple layers of neurons were formed, many of the neurons growing with no attachment to the crystalline surfaces. The neurons developed mature synaptic connections, with presynaptic sites expressing the synaptic vesicle protein 2 and postsynaptic sites having the shape of dendritic spines and expressing type 1 glutamate receptors, as these cells do under conventional culture conditions. The findings of the present study suggest that neuronal networks growing in a strong 3D aragonite support may find application as tissue replacement material for the central nervous system.

Altered regulation of brain-derived neurotrophic factor protein in hippocampus following slice preparation

Brain-derived neurotrophic factor (BDNF) and its cognate receptor tyrosine kinase B (TrkB) play important roles in regulating survival, structure, and function of CNS neurons. One method of studying the functions of these molecules has utilized in vitro hippocampal slice preparations. An important caveat to using slices, however, is that slice preparation itself might alter the expression of BDNF, thereby confounding experimental results. To address this concern, BDNF immunoreactivity was examined in rodent slices using two different methods of slice preparation. Rapid and anatomically selective regulation of BDNF content followed slice preparation using both methodologies; however, different patterns of altered BDNF immunoreactivity were observed. First, in cultured slices, BDNF content decreased in the dentate molecular layer and increased in the CA3 pyramidal cell layer and the mossy fiber pathway of the hippocampus after 30 min. Furthermore, an initially “punctate” pattern of BDNF labeling observed in the mossy fiber pathway of control sections changed to homogenous labeling of the pathway in vitro. In contrast to these findings, slices prepared as for acute slice physiology exhibited no change in BDNF content in the molecular layer and mossy fiber pathway 30 min after slicing, but exhibited significant increases in the dentate granule and CA3 pyramidal cell layers. These findings demonstrate that BDNF protein content is altered following slice preparation, that different methods of slice preparation produce different patterns of BDNF regulation, and raise the possibility that BDNF release and TrkB activation may also be regulated. These consequences of hippocampal slice preparation may confound analyses of exogenous or endogenous BDNF on hippocampal neuronal structure or function.

Neuron loss and axon reorganization in the dentate gyrus of cats infected with the feline immunodeficiency virus

The pathophysiological bases of cognitive, motor, and behavioral abnormalities in patients infected with the human immunodeficiency virus (HIV-1) remain largely unknown. To test the possibility that changes in hippocampal neuronal structure may contribute to these neurologic abnormalities, we examined the brains of cats infected with the feline immunodeficiency virus (FIV), an animal model of HIV-1 infection. We evaluated the dentate gyrus by using Timm's staining to estimate the extent of granule cell axon reorganization and by using Nissl staining, immunocytochemistry, and the optical fractionator method to estimate changes in the number of different neuronal subtypes. FIV-infected cats had abnormally high amounts of Timm's staining in the inner molecular layer and granule cell layer and loss of Nissl-stained, somatostatin-immunoreactive, and parvalbumin-immunoreactive neurons in the hilus. An inverse correlation existed between hilar neuron numbers and extent of aberrant Timm's staining. Increased Timm's staining and hilar neuron loss occurred throughout the septotemporal axis of the hippocampus. This type of neuronal loss and synaptic reorganization may provide an anatomic basis for some of the neurologic symptoms found in FIV-infected cats and HIV-infected humans. J. Comp. Neurol. 411:563–577, 1999. © 1999 Wiley-Liss, Inc.

Neuron loss and axon reorganization in the dentate gyrus of cats infected with the feline immunodeficiency virus

The pathophysiological bases of cognitive, motor, and behavioral abnormalities in patients infected with the human immunodeficiency virus (HIV-1) remain largely unknown. To test the possibility that changes in hippocampal neuronal structure may contribute to these neurologic abnormalities, we examined the brains of cats infected with the feline immunodeficiency virus (FIV), an animal model of HIV-1 infection. We evaluated the dentate gyrus by using Timm's staining to estimate the extent of granule cell axon reorganization and by using Nissl staining, immunocytochemistry, and the optical fractionator method to estimate changes in the number of different neuronal subtypes. FIV-infected cats had abnormally high amounts of Timm's staining in the inner molecular layer and granule cell layer and loss of Nissl-stained, somatostatin-immunoreactive, and parvalbumin-immunoreactive neurons in the hilus. An inverse correlation existed between hilar neuron numbers and extent of aberrant Timm's staining. Increased Timm's staining and hilar neuron loss occurred throughout the septotemporal axis of the hippocampus. This type of neuronal loss and synaptic reorganization may provide an anatomic basis for some of the neurologic symptoms found in FIV-infected cats and HIV-infected humans.

Monoclonal antibodies specifically recognizing granular structures in hippocampal neurons

Monoclonal antibodies specifically recognizing granular structures in hippocampal neurons