Dentate Fascia Research Articles

Frontotemporal dementia: Addressing the scattered harbingers of genetics and its relationship with glucose metabolism, bipolar disorder, and amyotrophic lateral sclerosis

Frontotemporal Dementia, also known by the name Pick's disease, is a rare form of dementia that can run for several generations. The two key characteristics are argyrophilic, spherical intraneuronal inclusions, which most frequently impact the frontal and temporal poles, and localized cortical atrophy (Pick bodies). Although personality decline and memory loss are frequently more severe than the visuospatial and apraxia disorders that are common in Alzheimer's disease, clinical overlap with other non-Alzheimer degenerative disorders is being increasingly recognized. The limbic system, which includes the hippocampus, entorhinal cortex, and amygdala, typically experiences the greatest levels of neuronal loss and degeneration. In the hippocampus's dentate fascia, several Pick bodies are frequently seen. Leukoencephalopathy and inflated cortical neurons are less specific symptoms (Pick cells). In this paper, we review the factors leading to Picks disease along with its pathophysiology, clinical manifestations, diagnosis, imaging, treatment, prognosis, and a comprehensive discussion on the same. We have also discussed the relationship of frontotemporal dementia with glucose metabolism, bipolar disorder, and amyotrophic lateral sclerosis, all of which are emerging fields of interest and need more studies.

Delayed Effects of Surgery during Early Pregnancy on Brain Development in OXYS Rats

The aim of the present work was to study the effects of stress induced by surgical interventions in early pregnancy on neuron density in the prefrontal cortex and hippocampal fields CA1 and CA3 and on neurogenesis in the dentate fascia of the hippocampus in the adult offspring of OXYS rats. Female OXTS rats were paired with fertile males of the same strain and, 96 h after detection of spermatozoids in vaginal smears, underwent a surgical procedure imitating embryo transplantation. The offspring of these females (OXYS-PS) were studied in comparison with intact OXYS and WAG rats aged five months. The density of pyramidal neurons in the prefrontal cortex of intact OXYS rats was significantly greater than that in rats of the WAG control strain. Neuron density in hippocampal field CA1 in intact OXYS rats was smaller, while that in field CA3 was greater, than that in WAG rats. No significant differences in the intensity of neurogenesis were seen between intact WAG and OXYS rats. In rats of the experimental group, OXYS-PS, the density of pyramidal neurons was lower in the prefrontal cortex and hippocampal field CA1 than in both control strains, while in field CA3 it was lower only in comparison with intact OXYS rats. In addition, rats of the OXYS-PS group showed a higher level of neurogenesis in the dentate gyrus of the hippocampus than both control strains.

Ultrastructural Alterations in Granular Neurons of the Dentate Fascia Caused by Intrahippocampal Injection of Beta-Amyloid 1-42.

The deposition of beta-amyloid (Aβ) in the brain is detected in Alzheimer's disease and during ageing. Until now, ultrastructural studies of changes caused by Aβ in the dentate gyrus are very scarce. The effects of Aβ 1-42 injection into the CA1 field of rat hippocampus were studied by electron microscopy. In 2 weeks after injection of aggregated Aβ in low concentrations, destructive changes were seen in the structure of dentate gyrus cells, which consisted in a decrease in the number of dentate gyrus neurons and axo-dendritic synapses. These changes were accompanied by enlargement of the endoplasmic reticulum cisterns and widening of the active zones of synapses. Thus, injection of aggregated Aβ 1-42 into the hippocampus led to irreversible (a decrease in the number of neurons and axo-dendritic synapses, agglutination of synthetic vesicles) and adaptive changes (an increase in the sizes of endoplasmic reticulum cisterns and active zones of synapses) in dentate gyrus neurons aimed at the maintenance of functional activity of the nervous system.

From the Entorhinal Region via the Prosubiculum to the Dentate Fascia: Alzheimer Disease-Related Neurofibrillary Changes in the Temporal Allocortex.

The pathological process underlying Alzheimer disease (AD) unfolds predominantly in the cerebral cortex with the gradual appearance and regional progression of abnormal tau. Intraneuronal tau pathology progresses from the temporal transentorhinal and entorhinal regions into neocortical fields/areas of the temporal allocortex. Here, based on 95 cases staged for AD-related neurofibrillary changes, we propose an ordered progression of abnormal tau in the temporal allocortex. Initially, abnormal tau was limited to distal dendritic segments followed by tau in cell bodies of projection neurons of the transentorhinal/entorhinal layer pre-α. Next, abnormal distal dendrites accumulated in the prosubiculum and extended into the CA1 stratum oriens and lacunosum. Subsequently, altered dendrites developed in the CA2/CA3 stratum oriens and stratum lacunosum-moleculare, combined with tau-positive thorny excrescences of CA3/CA4 mossy cells. Finally, granule cells of the dentate fascia became involved. Such a progression might recapitulate a sequence of transsynaptic spreading of abnormal tau from 1 projection neuron to the next: From pre-α cells to distal dendrites in the prosubiculum and CA1; then, from CA1 or prosubicular pyramids to CA2 principal cells and CA3/CA4 mossy cells; finally, from CA4 mossy cells to dentate granule cells. The lesions are additive: Those from the previous steps persist.

The Effect of a Single Heating Treatment on Laboratory Mice Behavior, Adult Neurogenesis, and the Expression of Heatshock Protein HSP-70

Male hybrid mice (F1 CBA × C57BL/6J) were kept for 1.5 h at 39.5°С. In cognitive tests (extrapolation and puzzle-box elementary logic task solution), mice of the experimental groups (after exposure to an elevated temperature) solved the tasks more quickly and more successfully, while their activity in the “small open field” (in which no stress-inducing stimuli were present) and in the Porsolt test (unescapable swimming) was higher than in control mice. In separate experiments, the temporary impairment in the adult neurogenesis (the decrease of new cell numbers detected immunо-histochemically by the marker Ki67) after elevated temperature exposure was demonstrated in both the subgranular area of dentate fascia and in the subventricular proliferative zone of the forebrain. The heating treatment was accompanied by the increase of HSP-70 expression at the time point 3 h after the treatment, while no differences from control were found after 24 h.

Structural Organization of Astrocytes in the Subgranular Zone of the Rabbit Hippocampal Dentate Fascia

Neurogenesis in the subgranular zone (SGZ) of the mammalian hippocampus is well known to occur throughout the life span. Astrocytes in this specialized proliferative zone are supposed to have properties of progenitor cells. Structural features of these cells and their interspecies differences remain understudied, while data on the structural organization of the SGZ in the rabbit (order Lagomorpha, superorder Glires), which is widely used in medical and biological studies, are lacking at all. The present work was focused on the structural and cytochemical organization of astrocytes in the SGZ of the rabbit hippocampal dentate fascia as studied by laser confocal microscopy. The study was carried out on the brain of adult Chinchilla rabbits compared to that of adult Wistar rats. Two morphological astrocyte types were identified in the rabbit SGZ: radial gliocyte-like (type I) and atypical fibrous astrocyte-like (type II) cells. By contrast, the rat SGZ exhibited a predominance of type II astrocytes which lacked long unramified processes penetrating through the granular layer and reaching the molecular layer. SGZ astrocytes, both in the rabbit and rat, were characterized by intense immunoreactivity for glutamine synthetase, most pronounced in the processes that formed the perivascular glia limitans. Importantly, the peculiarities of the astrocyte organization in the dentate fascia of the rabbit hippocampus allowed SGZ delimitation, whereas astrocytes in the rat SGZ exhibited no local morphological distinctions. The latter finding indicates a more complex organization of the neurogenic zone in the hippocampus of lagomorphs in contrast to the same zone in rodents.

Hippocampal Sclerosis in the Oldest Old: A Finnish Population-Based Study.

Background:There are only few population-based studies that have systemically investigated the prevalence of hippocampal sclerosis (HS) in the very old. The frequency of unilateral versus bilateral HS has been rarely studied.Objective:We investigated the prevalence and laterality of HS and its association with other neurodegenerative and vascular pathologies in a population-based sample of very elderly. Furthermore, the concomitant presence of immunoreactivity for TDP-43, p62, and HPtau was studied.Methods:The population-based Vantaa 85+ study includes all inhabitants of the city of Vantaa, who were >85 years in 1991 (n = 601). Neuropathological assessment was possible in 302 subjects. Severity of neuronal loss of CA sectors and subiculum was determined bilaterally by HE- staining. Immunohistochemistry performed using antibodies for TDP-43, p62, and HPtau.Results:Neuronal loss and pathological changes in the hippocampus sector CA1 and subiculum were observed in 47 of the 302 individuals (16%), and 51% of these changes were bilateral. HS without comorbid neurodegenerative pathology was found in 1/47 subjects with HS (2%). Dementia (p < 0.001) and TDP-43 immunopositivity of the granular cell layer of the dentate fascia (p < 0.001) were strongly associated with HS. The CERAD score, immunopositivity for HPtau and p62 in the granular cell layer of the fascia dentate were also associated.Conclusion:HS is prevalent (16%) in the oldest old population, but HS without any comorbid neurodegenerative pathology is rare. The high frequency of unilateral HS (49%) implied that bilateral sampling of hippocampi should be routine practice in neuropathological examination.

Influence of "Enriched Environment" on Behavior and Neurogenesis in Mice Selected by Cognitive Trait.

Mice selected for high score in the extrapolation test (EX line) and kept under conditions of "enriched environment" for 3 months demonstrated changes in locomotor and exploratory activity and enhanced reaction to novelty. The relative brain weight was higher and neurogenesis in the hippocampal fascia dentate was more intensive in this group. In non-selected mice, the changes were similar, but insignificant in many cases.

Distribution of GAD67-expressing neurons and morphological changes in hippocampal structures during pubertal period after acute perinatal hypoxia in rats

We investigated structural changes in the Wistar rat hippocampal CA1 field and fascia dentate during the pubertal period (on P60) after perinatal hypoxic exposure as well as the distribution of GAD67-expressing neurons in these structures. It was established that in the granular layer of the fascia dentata and in the CA1 field acute perinatal hypoxia leads to irreversible homotypic abnormalities as expressed in the reduced number of neurons and their rows as well as injury of a considerable portion of cells, which exhibit the signs of chromatolysis and vacuolization of the cytoplasm. Both in experimental and control animals, GAD67-expressing neurons in the fascia dentata are scattered diffusely and share approximately the same size of their populations. In the CA1 field, immunoreactive neurons lie in the lower rows of the pyramidal layer, while neurons in the upper layers exhibit no immunolabeling and have less synaptic structures in experimental animals than in control. We suggest that neurons in the hippocampal structures are involved in the regulation of functions and formation of prenatal pathology.

Clinicopathologic heterogeneity in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) due to microtubule-associated protein tau (MAPT) p.P301L mutation, including a patient with globular glial tauopathy.

The p.P301L mutation in microtubule-associated protein tau (MAPT) is a common cause of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We compare clinicopathologic features of five unrelated and three related (brother, sister and cousin) patients with FTDP-17 due to p.P301L mutation. Genealogical, clinical, neuropathologic and genetic data were reviewed from eight individuals. The series consisted of five men and three women with an average age of death of 58 years (52-65 years) and average disease duration of 9 years (3-14 years). The first symptoms were those of behavioural variant frontotemporal dementia in seven patients and semantic variant of primary progressive aphasia in one. Three patients were homozygous for the MAPT H1 haplotype; five had H1/H2 genotype. The apolipoprotein E genotype was ϵ3/ϵ3 in seven and ϵ3/ϵ4 in one. The average brain weight was 1015 g (876-1188 g). All had frontotemporal lobar or more diffuse cortical atrophy. Except for one patient, the hippocampus and parahippocampal gyrus had minimal atrophy, whereas there was atrophy of middle and inferior temporal gyri. Dentate fascia neuronal dispersion was identified in three patients, two of whom had epilepsy. In one patient there was extensive white matter tau involvement with Gallyas-positive globular glial inclusions typical of globular glial tauopathy (GGT). This clinicopathologic study shows inter- and intra-familial clinicopathologic heterogeneity of FTDP-17 due to MAPT p.P301L mutation, including GGT in one patient.

Treatment of odontoid fractures using percutaneous cannulated screwing with the help of a novel aiming device

Objective To evaluate the clinical efficacy of a self-designed novel n-shaped aimingdevice in aiding the percutaneous cannulated screwing for treatment of odontoid fractures of Anderson-D’Alonzo type II and shallow type Ⅲ. Methods A retrospective analysis was conducted of the 17 patients who had been treated at our department for odontoid fracture of Anderson-D' Alonzo type II and shallow type Ⅲbetween January 2009 and December 2013. They were 13 males and 4 females, with an average age of 37. 5years(from 16 to 61 years). All received surgical treatment after skull traction or jaw pillow traction preoperatively for reduction. Intraoperatively, percutaneous cannulated screwing via the anterior cervical approach was performed with the help of a self-designed novel n-shaped aiming device to fix the odontoid. Postoperatively, X-ray and CT scan were used to check the screw locations and evaluate the fracture healing. Results The 17 cases were followed up for 6 to 15 months(average, 10. 5 months). No intraoperative injury to the esophagus, artery, spinal cord or nerve root happened. The operating time ranged from 60 to 125 min. The bleeding was from 10 to 40 mL. Intraoperative observation revealed fine locations of the screws. Bony union was achieved in 16 cases 3 months postoperatively while separation and hardening of the fracture ends was found in one case. Conclusion Our self-designed novel n-shaped aiming device can facilitate the percutaneous cannulated screwing for treatment of odontoid fractures of Anderson-D'Alonzo type II and shallow type Ⅲ, given that it has advantages of simple manipulation, accurate insertion, minimal invasion, quick recovery and reliable efficacy. Key words: Fascia dentate; Fractures, bone; Fracture fixation, internal; Aiming device

A genetic context for the study of audiogenic seizures.

Here, the genetic context for the study of audiogenic seizures is four single-gene, spontaneous mutations that occurred in the Behavior Genetics Laboratory at the University of Chicago from 1959 to 1969. Three of these increased the incidence of audiogenic seizures, and one of these decreased the incidence of audiogenic seizures. The genetics of one of these mutants is described in detail, and the effect of diet on the same mutant is also described in detail. Research on genetic and environmental effects on the cortical EEG of audiogenic seizures is reviewed; this research included two of these mutants. The cortical EEG associated with audiogenic seizures in this study was consistent with audiogenic seizures being a type of brain stem epilepsy as had been proposed by others. Also, I proposed that brain stem pathophysiology is the same regardless of the genetic or environmental pathway to audiogenic seizure susceptibility. Research is also reviewed using these mutants to determine whether or not a strain association between glutamic acid decarboxylase (GAD) activity in whole brain and susceptibility to audiogenic seizures is pleiotropic and whether or not a strain association between nucleoside triphosphatase (NTPase) activity in the granule cell layer of the dentate fascia of the hippocampus and susceptibility to audiogenic seizures is a lineal or collateral pleiotropy. Lastly, pleiotropy as an explanation for strain comorbidities in aggressive behavior and audiogenic seizures is considered. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".

Structural organization of glial cells at the border between the neurotransplant and recipient brain.

Integration of fetal hippocampal dentate fascia neurotransplants with the neocortical somatosensory region in adult rats was studied by electron microscopy. The growth of nerve fiber through the neurotransplant/brain border formed by the glial cells was studied. The interface zone was organized by various astrocyte subpopulations and ependymocytes forming multilamellar accumulations in some sites of the interface. These conglomerations of the glial cells and their processes did not prevent the growth of axonal and axodendritic bundles; moreover, fibrous astrocyte axons accompanied them. Under conditions of immature nervous tissue transplantation to the focus of mature brain damage, the glial cells created a substrate in the interface permeable for nerve fibers, thus promoting the functional integration of the neurotransplant.

A novel α-synuclein mutation A53E associated with atypical multiple system atrophy and Parkinson's disease-type pathology

We describe the clinical, neuropathological, and genetic features of a Finnish patient with a novel α-synuclein (SNCA) mutation A53E. The patient was clinically diagnosed with atypical Parkinson's disease (PD) with age of onset at 36 years. In the neuropathological analysis performed at the age of 60 years, highly abundant SNCA pathology was observed throughout the brain and spinal cord showing features of multiple system atrophy and PD. Neuronal and glial (including oligodendroglial) SNCA inclusions and neurites were found to be particularly prominent in the putamen, caudatus, amygdala, temporal and insular cortices, gyrus cinguli, and hippocampus CA2-3 region. These areas as well as the substantia nigra and locus coeruleus showed neuronal loss and gliosis. We also found TDP-43 positive but mostly SNCA negative perinuclear inclusions in the dentate fascia of the hippocampus. The A53E mutation was found in 2 other relatives who had parkinsonism. Our results suggest that the novel SNCA A53E substitution is a causative mutation resulting clinically in parkinsonism and pathologically in severe multiple system atrophy- and PD-type phenotype.

Reactive Changes in the Microglia in the Neocortex and Hippocampus in Rats after Acute Prenatal Hypoxia

The dynamics of reactive changes in the population density of microgliocytes and the reversibility of their phenotypic forms were studied in the brains of neonatal rats at different time points after acute 1-h exposure to normobaric hypoxia in a barochamber on postnatal day 2. Different parts of the neocortex (frontal, motor, somatosensory, and visual) and segments of the hippocampus (fields CA1, CA3, and CA4 and the dentate fascia) were studied at 1 and 3 h and 1 and 5 days after hypoxia. Microgliocytes were detected immunocytochemically using polyclonal antibodies to Iba-1 antigen. The results showed that the microglial reactions to acute hypoxia in the neocortex and hippocampus in neonates developed simultaneously and synchronously with increases in cell death. Increases in the population density of ameboid microgliocytes in the brain areas of interest occurred within 1 h and resulted from migration of these cells from the subventricular zone and areas adjacent to the major vessels, where they virtually disappeared. The numbers of ameboid microgliocytes in these areas recovered quite quickly (within 3 h). The population density of microgliocytes, especially those of the ameboid form, increased sharply with increases in cell death and lasted to five days.

Structural signs of dynamic state of synaptic contacts between neurotransplant and brain.

We studied ultrastructure of synaptic connections between long-living dentate fascia transplants and somatosensory area of the neocortex in rats. Giant synaptic terminals of granular neurons upon contact with unusual neuronal targets in the neocortex reproduced their specific constitutive morphological features. At the same time, developing synapses with signs of active structural and metabolic reorganization were revealed. This is indicative of a dynamic state and instability of functional connections between the transplant and brain despite long time after transplantation.

Inductive role of mossy fibers of hippocampus in the development of dendritic spines in aberrant synaptogenesis at neurotransplantation

The dentate fascia of the hippocampal formation isolated from 20-day-old Wistar rat fetuses was subjected to heterotopic transplantation into the somatosensory area of the neocortex of adult rats of the same strain. Five months after surgery, neurotransplantates, together with neighboring area of the neocortex, were studied using light and electron microscopy. We carried out a detailed study of the ultrastructure of the ectopic synaptic endings formed by the axons of granular neurons of the dentate fascia (mossy fibers) with neurons of the neocortex unusual for them in a normal state. Ultrastructural analysis revealed that most ectopic synaptic endings produce its determinant morphological features: giant sizes ofpresynaptic knobs, active zones with branched dendritic spines, and adherens junctions with the surface of dendrites. The data indicate that the mossy fibers growing from neurotransplantates induce structural and chemical reorganization of dendrites of the neocortex using transmembrane adherens junctions, such as puncta adherentia junctions. This results in the differentiation of active zones and development of dendritic spines typical for giant synaptic endings that are invaginated into presynaptic endings. Thus, the ability of neurons of the dentate fascia to form aberrant synaptic connections at transplantation results from the inductive synaptogenic properties of mossy fibers.

Deflective placement of anterior odontoid cannulated screw for treatment of odontoid fracture combined with atlantoaxial posterior dislocation

Objective To investigate deflective placement of anterior odontoid cannulated screw for treatment of odontoid fracture combined with atlantoaxial posterior dislocation.Method From August 2002 to December 2011,18 cases of fresh odontoid fracture combined with atlantoaxial posterior dislocation were treated with deflective placement of anterior odontoid cannulated screw in our hospital.They were 10 males and 8 females,aged from 20 to 50 years (mean,41 years).According to the classification of Anderson-D'Alonzon,12 cases were type Ⅱ and 6 type Ⅲ; according to the classification of American Spinal Injury Association (ASIA),3 cases were grade C,10 grade D and 5 grade E.All patients underwent skull traction pre-operation to reduce dislocation.During the operation,the head was bent close to the chest in order to maintain atlantoaxial restoration and odontoid reduction.Because in this posture the jawbone blocked Kirschner wire and made the placement challenging,the anterior odontoid cannulated screw was deflected in all cases.Results In this series,the operation time ranged from 1.0 to 1.5 hours and the blood loss 50 to 100 mL (mean,75 mL).The mean time of follow-up was 15 months (range,12 to 18 months).All cases got bony union 3 to 4 months postoperation without screw failure.According to the ASIA grading for neural function,one case improved from grade C to grade E,one from grade C to grade D,9 cases from grade D to grade E,and no improvement was noted in the other cases.The difference in atlantoaxial shift distance between preoperation and postoperation was statistically significant (P ＜ 0.05).Conclusion In the treatment of odontoid fracture combined with atlantoaxial posterior dislocation,deflective placement of anterior odontoid cannulated screw may preserve the rotation function of the atlas and axis and lead to positive outcomes. Key words: Fascia dentate; Atlanto-axial joint; Fracture, bone; Dislocation ; Fracture fixation, internal

Long-Term Consequences of Hypoxia During the Perinatal Period of Development on the Structural-Functional Characteristics of the Brain in Rats

The experiments reported here showed that acute hypoxia during the perinatal period of development leads to structural changes in the motor and visual areas of the neocortex, detectable by postnatal day 20 as impairments to the structural organization of the layers of the neocortex. We report the first data showing that different hippocampal fields respond differently to hypoxia during the postnatal period and present evidence for the existence of long-term sequelae of perinatal hypoxia in the structure of the hippocampus. Acute hypoxia was followed by cell death in all fields and thinning of the pyramidal neuron layers. The greatest levels of cell death occurred in fields CA4 and CA3. As postnatal age increased, cell death remained significant in field CA4, decreased in field CA3, and was not seen in field CA1, though granule neuron death in the dentate fascia increased with increasing age. In addition, there were decreases in the sizes of pyramidal neuron cell bodies in all hippocampal fields. All hippocampal fields showed activation of astrocyte reactions, more marked in field CA4, where gliosis persisted to prepubertal age. Hypoxia in the early postnatal period could have effects on synaptogenesis, particularly on the formation of giant synapses in the dentate fascia. Studies of the functional characteristics of the nervous system in such animals showed that hypoxia could induce significant impairments in behavioral reactions. Rats of the experimental group showed impairments to the inhibitory functions of the cerebral cortex, increased anxiety, and disturbances to spatial learning and working memory.

Inhomogeneous Rostrocaudal Activation of the Hippocampus in Mice after Exploration of a Novel Space

Hippocampal activity in C57BL/6 mice was studied during exploration of novel spaces of different levels of complexity and learning by neuromapping using the induction of c-Fos protein by nervous activity. c-Fos-immunopositive neurons were counted at eight levels along the whole of the rostrocaudal axis of the hippocampus. In experiment 1, mice were given six opportunities on a single day to find the entrance to the home cage through one of the arms of a modified eight-arm radial maze. Animals of the active control group were released into the home cage via an isolated arm. Mice tested in the eight-arm maze showed an inhomogeneous increase in c-Fos expression along the rostrocaudal axis: activation in the caudal part of fields CA1 and CA3 and the dentate fascia was significantly greater than that in the rostral part. In experiment 2, animals were tested in a novel open field. In this situation, the increase in expression in the caudal part of field CA1 was greater than that in the rostral part, though in field CA3 and the dentate fascia there was uniform activation over the whole rostrocaudal extent. Both experiments identified positive correlations between the density of c-Fos-positive neurons and measures of investigative activity. These data provide evidence that placing of animals in a novel space leads to inhomogeneous activation of the hippocampal field along its rostrocaudal axis.