Photobiomodulation reduces gliosis in the basal ganglia of aged mice

This study explored the effects of long-term photobiomodulation (PBM) on the glial and neuronal organization in the striatum of aged mice. Mice aged 12 months were pretreated with PBM (670 nm) for 20 minutes per day, commencing at 5 months old and continued for 8 months. We had 2 control groups, young at 3 months and aged at 12 months old; these mice received no treatment. Brains were aldehyde-fixed and processed for immunohistochemistry with various glial and neuronal markers. We found a clear reduction in glial cell number, both astrocytes and microglia, in the striatum after PBM in aged mice. By contrast, the number of 2 types of striatal interneurons (parvalbumin+ and encephalopsin+), together with the density of striatal dopaminergic terminals (and their midbrain cell bodies), remained unchanged after such treatment. In summary, our results indicated that long-term PBM had beneficial effects on the aging striatum by reducing glial cell number; and furthermore, that this treatment did not have any deleterious effects on the neurons and terminations in this nucleus

New Mouse Lines for the Analysis of Neuronal Morphology Using CreER(T)/loxP-Directed Sparse Labeling

BACKGROUND: Pharmacologic control of Cre-mediated recombination using tamoxifen-dependent activation of a Cre-estrogen receptor ligand binding domain fusion protein [CreER(T)] is widely used to modify and/or visualize cells in the mouse. METHODS AND FINDINGS: We describe here two new mouse lines, constructed by gene targeting to the Rosa26 locus to facilitate Cre-mediated cell modification. These lines should prove particularly useful in the context of sparse labeling experiments. The R26rtTACreER line provides ubiquitous expression of CreER under transcriptional control by the tetracycline reverse transactivator (rtTA); dual control by doxycycline and tamoxifen provides an extended dynamic range of Cre-mediated recombination activity. The R26IAP line provides high efficiency Cre-mediated activation of human placental alkaline phosphatase (hPLAP), complementing the widely used, but low efficiency, Z/AP line. By crossing with mouse lines that direct cell-type specific CreER expression, the R26IAP line has been used to produce atlases of labeled cholinergic and catecholaminergic neurons in the mouse brain. The R26IAP line has also been used to visualize the full morphologies of retinal dopaminergic amacrine cells, among the largest neurons in the mammalian retina. CONCLUSIONS: The two new mouse lines described here expand the repertoire of genetically engineered mice available for controlled in vivo recombination and cell labeling using the Cre-lox system

Development of catecholaminergic, indoleamine-accumulating and NADPH- diaphorase amacrine cells in rabbit retinae

We have investigated the ontogeny of four classes of amacrine cells in the rabbit retina. In particular, the distribution, number, soma diameter, dendritic field diameter, and pattern of dendritic stratification were studied in catecholaminergic (CA) and indoleamine‐accumulating (IA) amacrines and in two classes of nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase amacrine cells. The first CA and IA cells are observed on the 27th postconceptional day (27PCD) and the first NADPH‐diaphorase cells on 28PCD. These first cells are concentrated in the central part of the visual streak, and at subsequent ages, cells in this part of the streak have larger somata and more mature dendritic fields than those elsewhere, supporting the notion that the peak density region is a developmentally advanced part of the retina. Throughout development, amacrine cells of all classes are concentrated in the visual streak, with their density reaching minima at the superior and inferior retinal margins. As their total number increases, the difference in cell density between the streak and the periphery decreases, presumably because proportionately more cells are added at the periphery. Their total number peaks around 42PCD, followed by a decline of 12–31% to adult values. Once the peak number of cells has been reached, the difference in cell density between the streak and periphery begins to increase. The rate of this increase is closely correlated with the increase in retinal area. This redistribution of amacrine cells, as well as a greater expansion of their dendritic fields in peripheral retina, is almost certainly the product of nonuniform retinal expansion. © 1992 Wiley‐Liss, Inc

Remote Photobiomodulation Treatment for the Clinical Signs of Parkinson's Disease: A Case Series Conducted during COVID-19

Objective: To assess whether remote application of photobiomodulation (PBM) is effective in reducing clinical signs of Parkinson's disease (PD). Background: PD is a progressive neurodegenerative disease for which there is no cure and few treatment options. There is a strong link between the microbiome-gut-brain axis and PD. PBM in animal models can reduce the signs of PD and protect the neurons from damage when applied directly to the head or to remote parts of the body. In a clinical study, PBM has been shown to improve clinical signs of PD for up to 1 year. Methods: Seven participants were treated with PBM to the abdomen and neck three times per week for 12 weeks. Participants were assessed for mobility, balance, cognition, fine motor skill, and sense of smell on enrolment, after 12 weeks of treatment in a clinic and after 33 weeks of home treatment. Results: A number of clinical signs of PD were shown to be improved by remote PBM treatment, including mobility, cognition, dynamic balance, spiral test, and sense of smell. Improvements were individual to the participant. Some improvements were lost for certain participants during at-home treatment, which coincided with a number of enforced coronavirus disease 2019 (COVID-19) pandemic lockdown periods. Conclusions: Remote application of PBM was shown to be an effective treatment for a number of clinical signs of PD, with some being maintained for 45 weeks, despite lockdown restrictions. Improvements in clinical signs were similar to those seen with the application of remote plus transcranial PBM treatment in a previous study. Clinical Trial Registration number: U1111-1205-2035

Improvements in clinical signs of Parkinson's disease using photobiomodulation: a prospective proof-of-concept study

Background: Parkinson's disease (PD) is a progressive neurodegenerative disease with no cure and few treatment options. Its incidence is increasing due to aging populations, longer disease duration and potentially as a COVID-19 sequela. Photobiomodulation (PBM) has been successfully used in animal models to reduce the signs of PD and to protect dopaminergic neurons. Objective: To assess the effectiveness of PBM to mitigate clinical signs of PD in a prospective proof-of-concept study, using a combination of transcranial and remote treatment, in order to inform on best practice for a larger randomized placebo-controlled trial (RCT). Methods: Twelve participants with idiopathic PD were recruited. Six were randomly chosen to begin 12 weeks of transcranial, intranasal, neck and abdominal PBM. The remaining 6 were waitlisted for 14 weeks before commencing the same�treatment. After the 12-week treatment period, all participants were supplied with PBM devices to continue home treatment. Participants were assessed for mobility, fine motor skills, balance and cognition before treatment began, after 4 weeks of treatment, after 12 weeks of treatment and the end of the home treatment period. A Wilcoxon Signed Ranks test was used to assess treatment effectiveness at a significance level of 5%. Results: Measures of mobility, cognition, dynamic balance and fine motor skill were significantly improved (p < 0.05) with PBM treatment for 12 weeks and up to one year. Many individual improvements were above the minimal clinically important difference, the threshold judged to be meaningful for participants. Individual improvements varied but many continued for up to one year with sustained home treatment. There was a demonstrable Hawthorne Effect that was below the treatment effect. No side effects of the treatment were observed. Conclusions: PBM was shown to be a safe and potentially effective treatment for a range of clinical signs and symptoms of PD. Improvements were maintained for as long as treatment continued, for up to one year in a neurodegenerative disease where decline is typically expected. Home treatment of PD by the person themselves or with the help of a carer might be an effective therapy option. The results of this study indicate that a large RCT is warranted

Widespread brain transcriptome alterations underlie the neuroprotective actions of dietary saffron

Dietary saffron has shown promise as a neuroprotective intervention in clinical trials of retinal degeneration and dementia and in animal models of multiple CNS disorders, including Parkinson's disease. This therapeutic potential makes it important to define the relationship between dose and protection and the mechanisms involved. To explore these two issues, mice were pre-conditioned by providing an aqueous extract of saffron (0.01% w/v) as their drinking water for 2, 5 or 10\ua0days before administration of the parkinsonian neurotoxin MPTP (50\ua0mg/kg). Five days of saffron pre-conditioning provided the greatest benefit against MPTP-induced neuropathology, significantly mitigating both loss of functional dopaminergic cells in the substantia nigra pars compacta (p\ua