Springer Science and Business Media LLC

Psychomotor disturbance has been identified as a key feature of psychotic disorders, with motor signs observed in upwards of 66% of unmedicated, first-episode patients. Aberrations in the cerebellum have been directly linked to sensorimotor processing deficits including processing speed, which may underly psychomotor disturbance in psychosis, though these brain-behavior-symptom relationships are unclear, in part due to within-diagnosis heterogeneity across these levels of analysis. In 339 psychosis patients (242 schizophrenia-spectrum, 97 bipolar with psychotic features) and 217 controls, we evaluated the relationship between cerebellar grey matter volume in the Yeo sensorimotor network and psychomotor disturbance (mannerisms and posturing, retardation, excitement of the Positive and Negative Syndrome Scale [PANSS]), as mediated by processing speed (assessed via the SCIP). Models included intracranial volume, age, sex, and chlorpromazine equivalents as covariates. We observed significant mediation by processing speed, with a small positive effect of the cerebellum on processing speed (ß = 0.172, p = 0.029, d = 0.24) and a medium negative effect of processing speed on psychomotor disturbance (ß = −0.254, p < 0.001, d = 0.60), with acceptable specificity and sensitivity suggesting this model is robust against unmeasured confounding. The current findings suggest a critical role of cerebellar circuitry in a well-established sensorimotor aberration in psychosis (processing speed) and the presentation of related psychomotor phenotypes within psychosis. Establishing such relationships is critical for intervention research, such as TMS. Future work will employ more dimensional measures of psychomotor disturbance and cognitive processes to capture normative and aberrant brain-behavior-symptom relationships and may also determine the magnitude of these relationships within subtypes of psychosis (e.g., disorganized behavior, catatonia).

We aimed to explore the altered functional connectivity patterns within cerebello-cerebral circuits in temporal lobe epilepsy (TLE) patients with and without focal to bilateral tonic–clonic seizures (FBTCS). Forty-two patients with unilateral TLE (21 with and 21 without FBTCS) and 22 healthy controls were recruited. We chose deep cerebellar nuclei as seed regions, calculated static and dynamic functional connectivity (sFC and dFC) in the patients with and without FBTCS and healthy controls, and compared sFC and dFC among the three groups. Correlation analyses were used to assess relationships between the significantly altered imaging features and patient clinical parameters. Compared to the group without FBTCS, the FBTCS group showed decreased sFC between the right dentate nuclei and left hemisphere regions including the middle frontal gyrus, superior temporal gyrus, superior medial frontal gyrus and posterior cingulate gyrus, and significantly increased dFC between the right interposed nuclei and contralateral precuneus. Relative to HCs, the FBTCS group demonstrated prominently decreased sFC between the right dentate nuclei and left middle frontal gyrus. No significant correlations between the altered imaging features and patient clinical parameters were observed. Our results suggest that the disrupted cerebello-cerebral FC might be related to cognitive impairment, epileptogenesis, and propagation of epileptic activities in patients with FBTCS.

Cái chết tế bào chương trình hay apoptosis là một quá trình quan trọng để hình thành cấu trúc tế bào bình thường của người lớn. Tuy nhiên, phân tích in vivo của apoptosis thần kinh chưa được phát triển tốt. Do đó, cái chết tế bào apoptosis của một hệ thống thần kinh hoặc một phần giải phẫu cụ thể trong một dòng đột biến là một mục tiêu quý giá để tìm hiểu về mối liên hệ giữa một gen và apoptosis thần kinh. Ataxia (ax) là một dòng chuột đột biến thần kinh lặn tự động. Chúng tôi gần đây đã nghiên cứu não bộ của những cá thể đồng hợp tử cho ataxia Jackson (ax J), một alen của ax, bằng cách sử dụng phương pháp TUNEL. Một số tế bào dương tính với TUNEL đã được quan sát thấy trong lớp tế bào hạt của tiểu não, vòng răng và củ khứu giác ở những bạn vật đồng kiểu hình bình thường (ax J /+ hoặc +/+) có độ tuổi từ 23-38 ngày. Tuy nhiên, ở những con chuột ax J /ax J bị ảnh hưởng, số lượng tế bào dương tính với TUNEL tăng đáng kể trong tiểu não, đặc biệt là trong lớp tế bào hạt (p < 0.05). Chuột ax J sẽ là một mô hình in vivo độc đáo cho các nghiên cứu về cơ sở di truyền của cái chết tế bào thần kinh apoptosis, và việc xác định gen ax là cần thiết để làm sáng tỏ cơ sở phân tử của apoptosis.

We described a 63-year-old Japanese female with genetically confirmed Huntington’s disease who showed unusual pathological findings in the cerebellum. This case exhibited typical neuropathological features as Huntington’s disease, including severe degeneration of the neostriatum and widespread occurrence of ubiquitin and expanded polyglutamine-positive neuronal intranuclear and intracytoplasmic inclusions. The cerebellum was macroscopically unremarkable; however, somatic sprouts and halo-like amorphous materials of Purkinje cell with a large amount of torpedoes were noteworthy. Furthermore, the Purkinje cells were found to have granular cytoplasmic inclusions. Somatic sprouting is a form of degenerated Purkinje cell exhibited in several specific conditions. Although this finding usually appeared in developmental brains, several neurodegenerative disorders, including Menkes kinky hair disease, familial spinocerebellar ataxia, acute encephalopathy linked to familial hemiplegic migraine, and several other conditions, have been reported showing sprouting from the soma of Purkinje cell. We propose that Huntington’s disease is another degenerative condition associated with these distinct neuropathological findings of Purkinje cell. Abnormally accumulated huntingtin protein in the cytoplasm could be related to the development of these structures.

The inositol 1,4,5-trisphosphate (IP3) receptor is highly expressed in cerebellar Purkinje cells and mediates conspicuous calcium release from intracellular calcium stores. Receptor stimulation, such as through mGluR1, activates the Gq–PLC pathway, which leads to IP3-induced calcium release and subsequent cellular responses, including cerebellar long-term depression in Purkinje cells. Recent studies have demonstrated the regulatory mechanisms of IP3 receptor, revealing activation via IP3 and Ca2+, inactivation via high concentrations of Ca2+, and modulation by various proteins that bind to the IP3 receptor. Novel calcium imaging techniques and caged compounds provide analysis of calcium signals at the single spine level in relation to the induction of long-term depression. Genetically encoded indicators for calcium or IP3 could provide alternate Ca2+ or IP3 imaging, in particular, for in vivo observations. IP3-induced calcium release participates in early development of dendritic branch formation, and loss-of-function mutations or hyper-activation could result various diseases. The IP3 receptor plays a central role in calcium signaling in Purkinje cells, affecting a wide variety of cellular functions, including development, plasticity, maintenance of synaptic functions, and cerebellar motor control.

The postnatal development of the cerebellum is accomplished via a series of cytogenetic and morphogenetic events encoded in the genome. To decipher the underlying genetic basis of these events we have systematized the spatio-temporal gene expression profiles during mouse cerebellar development in the Cerebellar Development Transcriptome Database (CDT-DB). Using the CDT-DB, Ca2+-dependent activator protein for secretion 2 (CAPS2 or CADPS2) was identified as a developmentally regulated gene that is predominantly expressed in cerebellar granule cells (GCs) with an expression peak around the first or second postnatal week. CAPS2 protein is concentrated in parallel fiber (PF) terminals and is associated with secretory vesicles containing brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). CAPS2 enhances release of BDNF and NT-3, both of which are essential for normal cerebellar development. CAPS2-deficient (CAPS2−/−) mice show reduced secretion of BDNF and NT-3; consequently, the cerebella of these mice exhibit developmental deficits, such as delayed development and increased cell death in GCs, fewer branched dendrites on Purkinje cells (PCs), and loss of the intercrural fissure. The PF-PC synapses have aberrant cytoarchitectures and electrophysiological properties. These abnormal cellular and morphological phenotypes are more severe around the cerebellar vermis, in which hypoplasia has been reported in autism patients. Moreover, CAPS2−/− mice had fewer cortical and hippocampal parvalbumin-positive interneurons and some autistic-like behavioral phenotypes. In the CAPS2 genes of some autistic patients an aberrant splicing variant and non-synonymous SNPs have been identified. These recent studies implicate CAPS2 in autism susceptibility. Therefore, CAPS2−/− mice will be a useful model animal in which to study aspects of the neuropathology and behaviors characteristic of developmental disorders.

The spatial organization of vestibulospinal (VS) reflexes, elicited by labyrinthine signals and related to head motion, depends on the direction of body tilt, due to proprioceptive neck afferents acting through the cerebellar anterior vermis. The responses of Purkinje cells located within this region to labyrinthine stimulation are modulated by the head-to-body position. We investigated, in urethane-anesthetized rats, whether a 90° leg-to-trunk displacement modifies the responses of corticocerebellar and vestibular nuclear neurons to the labyrinthine input, which would indicate that VS reflexes are tuned by the leg-to-trunk position. With this aim, unit activity was recorded during “wobble” stimuli that allow evaluating the gain and spatiotemporal properties of neuronal responses. The response gain of corticocerebellar units showed a significant drop in the leg-rotated position with respect to the control one. Following a change in leg position, a proportion of the recorded neurons showed significant changes in the direction and phase of the response vector. In contrast, vestibular nuclear neurons did not show significant modifications in their response gain and direction. Thus, proprioceptive afferents signaling leg-to-trunk position seem to affect the processing of directional labyrinthine signals within the cerebellar cortex.