Enhanced anxiety-like behavior induced by chronic neuropathic pain and related parvalbumin-positive neurons in male rats.

Anxiety commonly co-occurs with and exacerbates pain, but the interaction between pain progression and anxiety, and its underlying mechanisms remain unclear. Inhibitory interneurons play a crucial role in maintaining normal central nervous system function and are suggested to be involved in pain-induced anxiety. This study aimed to elucidate the time-dependent effects of neuropathic pain on the developmental anxiety-like behaviors and related inhibitory interneurons; parvalbumin (PV)- and cholecystokinin (CCK)-positive neurons in corticolimbic regions. Using an 8-week-old male Wistar rat model with partial sciatic nerve ligation (pSNL), anxiety-like behaviors were biweekly assessed post-surgery through open field (OF) and elevated plus maze (EPM) tests. From 4 weeks post-surgery, pSNL rats exhibited reduced OF center time, rearing, and initial activity, along with diminished EPM open-arm activities (time spent, head dips, movement, and rearing), which correlated with the paw withdrawal threshold. These effects were absent at 2 weeks post-surgery. At 8 weeks post-surgery, specific behaviors (decreased total rearing and increased inactive time in EPM) were observed in the pSNL group. Immunohistochemistry revealed changes in PV- and CCK-positive neurons in specific corticolimbic subregions of pSNL rats at 8 weeks post-surgery. Notably, PV-positive neuron densities in the basolateral amygdaloid complex (BLC) and hippocampal cornu ammonis areas 1 and 2 correlated with anxiety-like behavioral parameters. PV-positive neurons in the BLC of pSNL rats were predominantly changed in large-cell subtypes and were less activated. These findings indicate that anxiety-like behaviors emerge in the late phase of neuropathic pain and relate to PV-positive neurons in corticolimbic regions of pSNL rats.

Coupled versus decoupled visuomotor feedback: Differential frontoparietal activity during curved reach planning on simultaneous functional near-infrared spectroscopy and electroencephalography.

INTRODUCTION: Interacting with the environment requires the planning and execution of reach-to-target movements along given reach trajectory paths. Human neural mechanisms for the motor planning of linear, or point-to-point, reaching movements are relatively well studied. However, the corresponding representations for curved and more complex reaching movements require further investigation. Additionally, the visual and proprioceptive feedback of hand positioning can be spatially and sequentially coupled in alignment (e.g., directly reaching for an object), termed coupled visuomotor feedback, or spatially decoupled (e.g., dragging the computer mouse forward to move the cursor upward), termed decoupled visuomotor feedback. During reach planning, visuomotor processing routes may differ across feedback types. METHODS: We investigated the involvement of the frontoparietal regions, including the superior parietal lobule (SPL), dorsal premotor cortex (PMd), and dorsolateral prefrontal cortex (dlPFC), in curved reach planning under different feedback conditions. Participants engaged in two delayed-response reaching tasks with identical starting and target position sets but different reach trajectory paths (linear or curved) under two feedback conditions (coupled or decoupled). Neural responses in frontoparietal regions were analyzed using a combination of functional near-infrared spectroscopy and electroencephalography. RESULTS: The results revealed that, regarding the cue period, curved reach planning had a higher hemodynamic response in the left SPL and bilateral PMd and a smaller high-beta power in the left parietal regions than linear reach planning. Regarding the delay period, higher hemodynamic responses during curved reach planning were observed in the right dlPFC for decoupled feedback than those for coupled feedback. CONCLUSION: These findings suggest the crucial involvement of both SPL and PMd activities in trajectory-path processing for curved reach planning. Moreover, the dlPFC may be especially involved in the planning of curved reaching movements under decoupled feedback conditions. Thus, this study provides insight into the neural mechanisms underlying reaching function via different feedback conditions.

Voluntary exercise reverses social behavior deficits and the increases in the densities of cholecystokinin-positive neurons in specific corticolimbic regions of diabetic OLETF rats.

Diabetes mellitus induces neuropsychiatric comorbidities at an early stage, which can be ameliorated by exercise. However, the neurobiological mechanisms underlying this ameliorative effect remain unclear. The present study was conducted in Otsuka Long-Evans Tokushima fatty (OLETF) rats, which develop diabetes with age, and aimed to investigate whether social and anxiety-like behaviors and neurobiological changes associated with these behavioral phenotypes were reversed by voluntary exercise and whether those were maintained in the later stage. We investigated the effects of exercise at different diabetic stages in OLETF rats by comparing with control rats. Three groups of OLETF rats were used: sedentary rats, rats exercising on a wheel for two weeks at 4-5 weeks of age (early voluntary exercise), and those exercising at 10-11 weeks of age (late voluntary exercise). In the elevated plus-maze test, both early and late voluntary exercises did not affect anxiety-like behavior. In the social interaction tests, both early and late voluntary exercises ameliorated impaired sociability, novel exploration deficits, and hypoactivity in OLETF rats. Both early and late voluntary exercises reversed the increases in cholecystokinin-positive neuron densities in the infralimbic cortex and hippocampal cornu ammonis area 3 in the OLETF rats, although they did not affect the area-reduction in the medial prefrontal cortex and the increase in cholecystokinin-positive neuron densities in the basolateral amygdala. These suggest that voluntary exercise has therapeutic effects on impaired sociability and novel exploration deficits associated with cholecystokinin-positive neurons in specific corticolimbic regions in OLETF rats, and those are maintained after early exercise.

Impact of Exercise and Detraining during Childhood on Brown Adipose Tissue Whitening in Obesity.

This study aimed to investigate the influence of childhood exercise and detraining on brown adipose tissue (BAT) whitening in obesity. Four-week-old male Long-Evans Tokushima Otsuka (LETO) rats (n = 9) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats (n = 24) were used as non-obese and obese animals, respectively. OLETF rats were divided into non-exercise sedentary (n = 9) and exercise groups. OLETF rats in the exercise group were further divided into subgroups according to the exercise period-exercise from 10- to 12-weeks-old (n = 6); and exercise from 4- to 6-weeks-old, and detraining from 6- to 12-weeks-old (n = 9). At 12-weeks-old, immediately after exercise period, BAT whitening in OLETF rats was inhibited by exercise despite the fact that hypertrophy was not caused in the plantaris muscle. However, the effectiveness was attenuated during the detraining period. Histological BAT whitening and downregulation of uncoupling protein-1 (UCP-1) were found in non-exercise sedentary OLETF rats at 12-weeks-old. The downregulation was not inhibited, even though exercise histologically inhibited BAT whitening in OLETF rats. Childhood exercise decreased BAT whitening in obesity. Detraining attenuated the inhibition of BAT whitening. These results suggest that regular exercise is needed to improve BAT whitening and downregulation of UCP-1 in obesity.

Medial prefrontal area reductions, altered expressions of cholecystokinin, parvalbumin, and activating transcription factor 4 in the corticolimbic system, and altered emotional behavior in a progressive rat model of type 2 diabetes.

Metabolic disorders are associated with a higher risk of psychiatric disorders. We previously reported that 20-week-old Otsuka Long-Evans Tokushima fatty (OLETF) rats, a model of progressive type 2 diabetes, showed increased anxiety-like behavior and regional area reductions and increased cholecystokinin-positive neurons in the corticolimbic system. However, in which stages of diabetes these alterations in OLETF rats occur remains unclear. We aimed to investigate anxiety-like behavior and its possible mechanisms at different stages of type 2 diabetes in OLETF rats. Eight- and 30-week-old OLETF rats were used as diabetic animal models at the prediabetic and progressive stages of type 2 diabetes respectively, and age-matched Long-Evans Tokushima Otsuka rats served as non-diabetic controls. In the open-field test, OLETF rats showed less locomotion in the center zone and longer latency to leave the center zone at 8 and 30 weeks old, respectively. The areas of the medial prefrontal cortex were smaller in the OLETF rats, regardless of age. The densities of cholecystokinin-positive neurons in OLETF rats were higher in the lateral and basolateral amygdala only at 8 weeks old and in the anterior cingulate and infralimbic cortices and hippocampal cornu ammonis area 3 at both ages. The densities of parvalbumin-positive neurons of OLETF rats were lower in the cornu ammonis area 2 at 8 weeks old and in the prelimbic and infralimbic cortices at both ages. No apoptotic cell death was detected in OLETF rats, but the percentage of neurons co-expressing activating transcription factor 4 and cholecystokinin and parvalbumin was higher in OLETF rats at both ages in the anterior cingulate cortex and basolateral amygdala, respectively. These results suggest that altered emotional behavior and related neurological changes in the corticolimbic system are already present in the prediabetic stage of OLETF rats.

Region-specific brain area reductions and increased cholecystokinin positive neurons in diabetic OLETF rats: implication for anxiety-like behavior.

Metabolic disorders can induce psychiatric comorbidities. Both brain and neuronal composition imbalances reportedly induce an anxiety-like phenotype. We hypothesized that alterations of localized brain areas and cholecystokinin (CCK) and parvalbumin (PV) expression could induce anxiety-like behavior in type 2 diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats. Twenty-week-old OLETF and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats were used. The areas of corticolimbic regions were smaller in OLETF rats. The densities of CCK positive neurons in the lateral and basolateral amygdala, hippocampal cornu ammonis area 2, and prelimbic cortex were higher in OLETF rats. The densities of PV positive neurons were comparable between OLETF and LETO rats. Locomotion in the center zone in the open field test was lower in OLETF rats. These results suggest that imbalances of specific brain region areas and neuronal compositions in emotion-related areas increase the prevalence of anxiety-like behaviors in OLETF rats.

Hemodynamic response during hyperbaric treatment on skeletal muscle in a type 2 diabetes rat model.

Mild hyperbaric treatment prevents type 2 diabetes progression due to increased oxygen concentration and blood flow in skeletal muscle. However, it remains unknown whether this treatment is effective during all stages of type 2 diabetes. This study aimed to investigate the influences of hyperbaric treatment at 1.3 atmospheres absolute (ATA) on hemodynamic response in various stages of type 2 diabetes. Otsuka Long-Evans Tokushima fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats were used as models of type 2 diabetes and healthy controls, respectively. Glucose levels were significantly higher in OLETF rats than in LETO rats at all ages. Glucose intolerance gradually increased with age in OLETF rats. Insulin levels in OLETF rats were significantly higher at 20-week-old, however, were significantly lower at 60-week-old than in LETO rats. Oxy-Hb, total Hb, and StO2 in skeletal muscle were increased during hyperbaric treatment in both rats. The hemodynamic changes were significantly higher in OLETF rats than LETO rats, and those changes were also pronounced at 8-week-old compared with other age in OLETF rats. These results suggest that hyperbaric treatment at 1.3 ATA acts on pathophysiological factors and the efficacy could be found only in the early stage of type 2 diabetes.

Case of asteroid hyalosis that developed severely reduced vision after cataract surgery.

BACKGROUND: To report our findings in a patient with asteroid hyalosis (AH) who had a severe reduction of his visual acuity following cataract surgery. The vision was improved by vitreous surgery. CASE PRESENTATION: The patient was an 81-year-old man. Following cataract surgery on his left eye, his decimal best-corrected visual acuity (BCVA) was markedly reduced from 0.2 to 0.02. A large number of asteroid bodies (ABs) was observed to be concentrated on the posterior surface of the implanted intraocular lens. Ultrasound B-mode images showed turbidity of the vitreous that was denser in the anterior vitreous where the ABs were concentrated. During vitrectomy, the ABs were observed to be concentrated in the anterior vitreous cavity, and a complete posterior vitreous detachment (PVD) was present. After vitrectomy successfully removed the ABs, the visibility of the fundus improved and the BCVA recovered to 1.0. CONCLUSION: We suggest that the visual impairment after the cataract surgery was due to the concentrated ABs in the anterior vitreous cavity. The clustering of the ABs in the anterior vitreous cavity was most likely caused by the PVD that developed during the cataract surgery.

A Case of Uveal Colobomas Showing Marked Left-Right Difference in Diabetic Retinopathy.

PURPOSE: Congenital uveal colobomas, including inferior iris and choroidal colobomas, are associated with microcornea and microphthalmia and often show left-right differences (laterality). The purpose of this study was to report a case of choroidal coloboma associated with left-right differences in diabetic retinopathy (DR). CASE: This study reports a 59-year-old male with bilateral iris and choroidal colobomas. The colobomatous area in the patient's right eye extended to the macula, and his right eye had been amblyopic since birth. The colobomatous area in his left eye was less extensive and did not involve the macula. Examination of the patient's left eye revealed multiple hemorrhages and hard exudates in the macula due to DR, but examination of his right eye showed almost no changes in DR, thus revealing a marked left-right difference. Optical coherence tomography showed more extensive retinal thinning in the patient's right eye than in his left eye. Fluorescein fundus angiography revealed a retinal nonperfusion area only in the left eye, and panretinal photocoagulation was subsequently performed. CONCLUSION: Our findings show that the reason for the left-right difference in DR was attributed to the more severe choroidal coloboma and retinal thinning in the patient's right eye compared to his left eye, thus reducing oxygen demand, as is also seen in eyes with severe myopia.

A Case of Coats' Disease with Spontaneous Retinal Reattachment after Total Detachment.

PURPOSE: To report a case of Coats' disease in which spontaneous reattachment occurred after total retinal detachment. PATIENT AND METHODS: A young boy (patient age: 4 years and 11 months) presented with leukocoria in the left eye. Slit-lamp examination revealed total retinal detachment with abnormal retinal blood vessels and subretinal exudation just behind the lens. Computed tomography imaging showed no solid mass lesion in the intraocular space. Secondary total retinal detachment as a complication of Coats' disease was diagnosed. No light perception was detected, so we determined that surgical treatment was not indicated. RESULTS: Four months after the initial diagnosis, the retina showed complete reattachment with a large amount of subretinal hard exudate. Visual acuity remained unchanged, with no light perception. CONCLUSIONS: We speculate that the spontaneous retinal reattachment in the present case was caused by the decreased permeability of the abnormal retinal vessels and the good functional effect of the retinal pigment epithelium.

[Case of retinal ischemia and retinal arteritis secondary to intravitreal nuclear drop].

BACKGROUND: A rare case of retinal arteritis and retinal ischemia as an incomplete branch retinal artery occlusion is reported following dropped lens fragments into the vitreous body. CASE: A 69 year-old-woman had a cataract OD with corrected visual acuity of 0.4. When she underwent phacoemulsification on March 11, the posterior capsule was damaged and nucleus fragments dropped into a vitreous body. A few days later, the vitreous opacity increased. The corrected visual acuity OD dropped to 0.06 due to anterior chamber inflammation and the intraocular pressure increased to 26 mmHg. During a pars plana vitrectomy on May 7, some retinal whitening were observed and incomplete branch retinal artery occlusion was confirmed by fluorescence fundus angiography. The corrected visual acuity finally improved to 0.3, but the right visual field defect remained. CONCLUSION: Incomplete branch retinal artery occlusion caused by phacoanaphylactic endophthalmitis secondary to lens fragments in the vitreous cavity seems to be a rare condition related to retinal whitening. The timing of pars plana vitrectomy should be considered before retinal arterial sheathing or retinal whitening can be noted.