Exosomes Secreted from Adipose-Derived Stem Cells Are a Potential Treatment Agent for Immune-Mediated Alopecia.

BACKGROUND: Alopecia has become an exceedingly prevalent dermatological disorder. Etiologically, infection (bacterial and fungal infection), inflammation, and immune dysregulation are the main causes of immune-mediated hair loss. Treating hair loss has remained challenging as the available therapies are limited. Exosomes from adipose-derived stem cells (ADSC-Exos) have been used for treating neurodegenerative diseases and autoimmune diseases and in wound-healing treatments. However, the function and mechanism of ADSC-Exos in alopecia treatment remain unclear. This study is aimed at investigating the effects of ADSC-Exos on hair growth in vitro and in vivo for potentially treating immune-mediated alopecia and further exploring the underlying mechanism. METHODS: Cell proliferation, migration, and apoptosis of dermal papilla cells (DPCs) that were treated with ADSC-Exos were detected using the cell counting kit-8 (CCK-8) assay, scratch wound-healing assay, and flow cytometry assay, respectively. A C57BL/6 hair-depilated mouse model was established in vivo; then, ADSC-Exos were subcutaneously injected alone or in combined with minoxidil. The effects of ADSC-Exos on hair growth, pathological changes, and the related mechanism were investigated by HE staining, quantitative real-time PCR (qRT-PCR), western blotting, and RNA sequencing (RNA-seq). RESULTS: ADSC-Exos significantly promoted DPC proliferation and migration while also reducing apoptosis. In addition, compared with the control group, ADSC-Exos-treated mice had better hair growth, more hair follicles (HFs) and thicker dermis. RNA-seq revealed that the miR-22 and TNF-α signaling pathways were markedly downregulated in DPCs after ADSC-Exos treatment. In addition, according to qRT-PCR and western blotting results, the Wnt/ß-catenin signaling pathway was activated in the skin of ADSC-Exos-treated mice. CONCLUSION: ADSC-Exos therapy positively affected the promotion of hair regrowth by regulating miR-22, the Wnt/ß-catenin signaling pathway, and the TNF-α signaling pathway, implying that ADSC-Exos could be a promising cell-free therapeutic strategy for immune-mediated alopecia.

A randomized blinded retrospective study: the combined use of micro-needling technique, low-level laser therapy and autologous non-activated platelet-rich plasma improves hair re-growth in patients with androgenic alopecia.

INTRODUCTION: Mini-invasive therapies based on autologous non-activated Platelet-Rich Plasma (ANA-PRP), Low-Level Laser Therapy (LLL-T), and Micro-Needling Technique (MN-T) used in combining for hair re-growth need to be standardized. OBJECTIVES: The work aims to show in vivo outcomes resulted from retrospective case-series study in which ANA-PRP + MN-T + LLL-T were used in combined in patients affected by Androgenic alopecia. METHODS: 23 patients were treated, of which 13 males were classified in stage I-V by the Norwood-Hamilton scale, and 10 females were classified in stage I-III by the Ludwig scale. Assessment of hair re-growth was evaluated with photography, physician's and patient's global assessment scale, and standardized phototrichograms during a follow-up: T0 - baseline, T1 - 12 weeks, T2 - 23 weeks, T3 - 44 weeks, T4 - 58 weeks. RESULTS: Interesting outcomes represented by a hair density increase of 81 ± 5 hairs/cm2 and 57 ± 7 hairs/cm2 respectively at T1 and T2 compared with baseline (173 ± 5 hairs/cm2 at T1 and 149 ± 9 hairs/cm2 at T2 versus 92 ± 2 hairs/cm2 at baseline) were observed using computerized trichograms. EXPERT OPINION: The main limitation in the autologous regenerative therapies and biotechnologies in hair-regrowth is the extreme variability of PRP products used, in the absence of standardized protocols and widely shared. Appropriate PRP preparations have to be pick after carefully thinking about their bio-molecular specifications and intended indications for use in patients. This approach will aid in matching the optimal PRP product to specific patient factors, leading to improved outcomes and the elucidation of the cost-effectiveness of this treatment. The combined use of biotechnologies as the association of PRP with micro-needling and low-level laser therapy may improve the results in terms of hair count and hair density compared with those obtained by alone PRP. All the procedures must be performed in the full respect of international and local rules. CONCLUSIONS: The effect of the combined use of MN-T, LLL-T, and ANA-PRP has been demonstrated.

Boehmite enhances hair follicle growth via stimulation of dermal papilla cells by upregulating ß-catenin signalling.

Hair growth, a complex process, has long been the subject of intense research. Recent developments in material technology have revealed boehmite as a new therapeutic modality for use in wound healing and scar reduction, indicating its beneficial effects. Nonetheless, the biological bases of the beneficial effects of boehmite remain unknown. We investigated the hair growth properties of boehmite in vitro and in vivo and observed dose-dependent proliferation of human dermal papilla cells (hDPCs) in vitro and hair regrowth in a mouse model. To investigate the effects of boehmite on the promotion of cell transition to the anagen phase, we evaluated hDPC viability, alkaline phosphatase (ALP) activity, protein expression and vascular endothelial growth factor (VEGF) secretion in vitro and assessed the anagen-promoting effects of boehmite via gross observation and histological analysis in a mouse model. Boehmite increased hDPC viability, ALP activity, AKT/GSK3ß/ß-catenin pathway activity, anagen-related gene expression and VEGF secretion; moreover, it accelerated hair regrowth in a catagen-anagen transition model via upregulation of ß-catenin signalling and follicular cell proliferation. Collectively, our results indicate that boehmite accelerates hair growth, partly via its effects on critical events in the active phase of the hair follicle cycle, including the promotion of the proliferation of hDPCs and their immediate progeny to the follicle base.

Herbal preparations for the treatment of hair loss.

Though hair does not serve any crucial physiological function in modern humans, it plays an important role in our self-esteem. Androgenic baldness (androgenic alopecia) and circular/spot baldness (alopecia areata) are the most common forms of hair loss. Many active ingredients of synthetic origin are available for treatment; however, they have a number of limitations. Their effectiveness and safety are questionable and the amount of time needed to achieve the effect is both long and unclear. This has increased interest in finding an alternative approach against hair loss using preparations containing plants and/or their isolated active ingredients. A number of studies (mostly randomized, placebo-controlled) of plants and preparations made of plants have been performed to confirm their effectiveness in treating hair loss. The plants with the most evidence-based effect against alopecia are Curcuma aeruginosa (pink and blue ginger), Serenoa repens (palmetto), Cucurbita pepo (pumpkin), Trifolium pratense (red clover), and Panax ginseng (Chinese red ginseng). The assumed mechanism of action is predominately inhibition of 5α-reductase, with enhanced nutritional support and scalp blood circulation playing a role as well.

Platelet-Rich Plasma as a Treatment for Androgenetic Alopecia.

BACKGROUND: Platelet-rich plasma (PRP) treatment may encourage hair growth by promoting cellular maturation, differentiation, and proliferation. OBJECTIVE: The objective of this study was to evaluate the effectiveness of PRP as a treatment for androgenetic alopecia (AGA). MATERIALS AND METHODS: A literature search combined with meta-analysis was used to calculate the overall standardized mean difference (SMD) in hair density in patients treated with PRP injections in comparison with baseline and placebo treatment. Chi squared analysis and Fisher exact test were used to investigate variation in protocols. RESULTS: The overall SMD in hair density was 0.58 (95% confidence interval [CI]: 0.35-0.80) and 0.51 (95% CI: 0.23-0.80, p < .0004) in favor of PRP treatment when compared with baseline and placebo treatment, respectively. CONCLUSION: Platelet-rich plasma is beneficial in the treatment of AGA. It is recommended that 3 monthly sessions of PRP (once monthly ×3 treatments) be used followed by a 3- to 6-month maintenance period.

Serenoa repens extracts promote hair regeneration and repair of hair loss mouse models by activating TGF-ß and mitochondrial signaling pathway.

OBJECTIVE: Plenty of plant extracts have been used for treating hair loss. This study aims to investigate the effects of liposterolic extracts of Serenoa repens (LSESr) on hair cell growth and regeneration of hair, and clarify the associated mechanisms. MATERIALS AND METHODS: Human keratinocyte cells (HACAT) were cultured, incubated with dihydrotestosterone (DHT) and treated with LSESr. Cell viability was examined by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H- tetrazolium bromide (MTT) assay. Hair loss C57BL/6 mouse model was established by inducing with DHT. Hair growth, density, and thickness were evaluated. Back skin samples were collected and stained with hematoxylin and eosin (HE) assay. B-cell lymphoma-2 (Bcl-2), Bcl-2 associated protein X (Bax), cleaved caspase 3 and transforming growth factor ß2 (TGF-ß2) were examined using Western blot assay. RESULTS: LSESr treatment significantly increased HACAT cell viabilities compared to DHT-only treated cells (p<0.05). LSESr treatment post injection of DHT significantly converted skin color from pink to gray and increased hair density, weight and thickness compared to DHT-only treated mice (p<0.05). LSESr treatment significantly triggered follicle growth and decreased inflammatory response. LSESr treatment significantly decreased TGF-ß2 and cleaved caspase 3 expression of hair loss mouse models compared to that of DHT treated mice (p<0.05). LSESr treatment significantly enhanced Bcl-2 expression and reduced Bax expression compared to that of DHT treated mice (p<0.05). Meanwhile, effects of LSESr were substantial even achieving to the potential of finasteride. CONCLUSIONS: LSESr promoted the hair regeneration and repair of hair loss mouse models by activating TGF-ß signaling and mitochondrial signaling pathway.

[What is the value of low-energie lasers in the treatment of androgenetic alopecia ?] / Quel est l'intérêt des lasers de basse énergie dans le traitement de l'alopécie androgéno-génétique ?

Male and female androgenetic alopecia is a common, chronic, psychologically stressful disorder affecting more than 50 % of the individuals by 50 years of age. Despite the current topical (minoxidil) or oral (the inhibitors of 5-? reductase finasteride or dutasteride) treatments, there is a need for more effective management options. The current clinical evidence, the possible mechanisms of action and the rare adverse events of the low level laser therapy in the treatment of androgenetic alopecia are presented.

L'alopécie androgéno-génétique est une pathologie très fréquente du cuir chevelu, touchant aussi bien l'homme que la femme et amenant souvent une détresse psychologique intense. Les traitements médicamenteux (minoxidil topique, inhibiteurs de la 5-? réductase per os) ne sont pas constamment efficaces et peuvent induire des effets secondaires significatifs. Le traitement local par laser de basse énergie est susceptible d'améliorer les résultats thérapeutiques, tant dans l'alopécie androgéno-génétique masculine que féminine. Les modes d'action de ce type de traitement, les résultats obtenus à ce jour dans les principales études cliniques et les rares manifestations indésirables sont présentés ici.

A matter of months: High precision migration chronology of a Bronze Age female.

Establishing the age at which prehistoric individuals move away from their childhood residential location holds crucial information about the socio dynamics and mobility patterns in ancient societies. We present a novel combination of strontium isotope analyses performed on the over 3000 year old "Skrydstrup Woman" from Denmark, for whom we compiled a highly detailed month-scale model of her migration timeline. When combined with physical anthropological analyses this timeline can be related to the chronological age at which the residential location changed. We conducted a series of high-resolution strontium isotope analyses of hard and soft human tissues and combined these with anthropological investigations including CT-scanning and 3D visualizations. The Skrydstrup Woman lived during a pan-European period characterized by technical innovation and great social transformations stimulated by long-distance connections; consequently she represents an important part of both Danish and European prehistory. Our multidisciplinary study involves complementary biochemical, biomolecular and microscopy analyses of her scalp hair. Our results reveal that the Skrydstrup Woman was between 17-18 years old when she died, and that she moved from her place of origin -outside present day Denmark- to the Skrydstrup area in Denmark 47 to 42 months before she died. Hence, she was between 13 to 14 years old when she migrated to and resided in the area around Skrydstrup for the rest of her life. From an archaeological standpoint, this one-time and one-way movement of an elite female during the possible "age of marriageability" might suggest that she migrated with the aim of establishing an alliance between chiefdoms. Consequently, this detailed multidisciplinary investigation provides a novel tool to reconstruct high resolution chronology of individual mobility with the perspective of studying complex patterns of social and economic interaction in prehistory.

Normal and aging hair biology and structure 'aging and hair'.

Much like an individual's hairstyle, hair fibers along the scalp see a number of changes over the course of one's lifetime. As the decades pass, the shine and volume synonymous with youthful hair may give way to thin, dull, and brittle hair commonly associated with aging. These changes are a result of a compilation of genetic and environmental elements influencing the cells of the hair follicle, specifically the hair follicle stem cells and melanocytes. Telomere shortening, decrease in cell numbers, and particular transcription factors have all been implicated in this process. In turn, these molecular alterations lead to structural modifications of the hair fiber, decrease in melanin production, and lengthening of the telogen phase of the hair cycle. Despite this inevitable progression with aging, there exists an array of treatments such as light therapy, minoxidil, and finasteride which have been designed to mitigate the effects of aging, particularly balding and thinning hair. Although each works through a different mechanism, all aim to maintain or potentially restore the youthful quality of hair.

Dietary copper supplementation improves pelt characteristics of female silver fox (Vulpes fulva) during the winter fur-growing season.

Copper has an essential role in normal fur pigmentation and fur quality. This study evaluated the effects of cupric citrate (CuCit) supplementation on growth, nutrients metabolism and pelt characteristics of the female silver fox (Vulpes fulva). Fifty age-matched female silver foxes with similar body weights were randomly divided into five dietary groups for 58 days during the winter fur-growing season. The basal diet contained 4.92 mg/kg copper. Groups I-V were supplemented with 6, 30, 60, 90 or 150 mg Cu from CuCit per 1 kg dry matter basal diet. Serum alkaline phosphatase activity was significantly higher (P<0.05) in those fed 90 mg/kg Cu than those fed 150 mg/kg Cu. Pelt total thickness was significantly higher (P<0.05) in those fed 30 mg/kg Cu than foxes fed 6 mg/kg Cu supplemented diet, but were similar to the other groups. Length of guard hair was significantly lower (P<0.05) in those fed 90 mg/kg Cu than fed 6 mg/kg Cu and 30 mg/kg Cu, but were similar to the other groups. Length of underhair was significantly higher (P<0.05) in those fed 6 mg/kg Cu than those fed 90 mg/kg Cu, but was similar to the other groups. Considering decreasing environmental contamination and improving pelt performance, supplementing 30 mg/kg Cu from CuCit (actual copper 35 mg/kg dry matter) is appropriate for female silver fox.

Effects of different dietary protein levels and DL-methionine supplementation on hair growth and pelt quality in mink (Neovision vision).

The effect of different dietary protein levels and DL-methionine (Met) supplementation on hair growth and the resulting pelt quality in mink was studied. Four groups of male mink were fed with four isocaloric diets containing 32% (P32), 24% (P24), 16% (P16) or P24+Met (0.8%) crude protein of dry matter (DM) from September to December. Skin biopsies were taken at the pelting. Histological techniques and computer-assisted light microscopy were used to determine the ratio of activity (ROA) of under hairs and guard hairs respectively. The results showed that when the dietary protein level reduced from 32% to 16%, body length, number and diameter of under hairs and guard hairs of minks declined, and pelt length and pelt weight of minks decreased significantly (p < 0.05). These parameters were similar between P32 and P24 with Met supplementation (p > 0.05). The hair follicle density of the winter coat was not influenced by the dietary protein levels and Met supplementation (p > 0.05). Low-protein diets content led to a reduction of hair follicle developing to next phase. It was documented that 24% crude protein of DM with Met supplementation during growing-furring period was sufficient for minks to express their genetic capacity to develop hair follicles and achieve the prime fur characteristics. Overall this study demonstrated that hair growth and hair properties in pelts are very dependent on the dietary protein and Met supply in the growing-furring period of minks.

Alopecia: a review of laser and light therapies.

Since the 1980s, laser technology has become increasingly popular to treat a variety of cutaneous conditions. Its successful use as an epilator comes with the rare but interesting side effect of paradoxical hypertrichosis. In this review, we summarize cases describing hair growth after photoepilation, as well as studies testing laser and light sources as treatment for alopecia, particularly androgenetic alopecia and alopecia areata. We also discuss the possible biologic mechanisms by which phototherapy induces hair regeneration.

Aero-tactile integration in speech perception.

Visual information from a speaker's face can enhance or interfere with accurate auditory perception. This integration of information across auditory and visual streams has been observed in functional imaging studies, and has typically been attributed to the frequency and robustness with which perceivers jointly encounter event-specific information from these two modalities. Adding the tactile modality has long been considered a crucial next step in understanding multisensory integration. However, previous studies have found an influence of tactile input on speech perception only under limited circumstances, either where perceivers were aware of the task or where they had received training to establish a cross-modal mapping. Here we show that perceivers integrate naturalistic tactile information during auditory speech perception without previous training. Drawing on the observation that some speech sounds produce tiny bursts of aspiration (such as English 'p'), we applied slight, inaudible air puffs on participants' skin at one of two locations: the right hand or the neck. Syllables heard simultaneously with cutaneous air puffs were more likely to be heard as aspirated (for example, causing participants to mishear 'b' as 'p'). These results demonstrate that perceivers integrate event-relevant tactile information in auditory perception in much the same way as they do visual information.

Effect of diet on mechanical properties of horse's hair.

The aim of this research was to assess the effect of diet supplementation with zinc and copper, in different chemical forms (organic and inorganic), on the mechanical properties of the hair of healthy English thoroughbred horses. Hairs were taken from 18 horses which had been fed with oats and hay for a period of 110 days. Twelve of the horses had been additionally given a daily dose of 700 g of highquality 44-ingredients Fohlengold St-Hippolyt muesli made by Muhle Ebert Dilheim. Six of them had received the muesli-containing organic zinc and copper (OS), while the other six horses had received the muesli-containing inorganic zinc and copper (IS). The mechanical properties of the hairs before and after the supplementation period were tested in a Synergie 100 (MTS) testing machine. Each of the hairs was loaded at a constant rate of 20 mm/min until rupture. Young modulus (E), breaking stress (Ru) and yield point (Rs) of the particular hairs were determined. No significant changes in the mechanical parameters were observed in the reference group in which the horses were fed with only oats and hay for the whole experimental period of 110 days. The supplementation of the diet with inorganic zinc and copper resulted in an increase in the elasticity and diameter of the hairs and in a simultaneous reduction in their strength. Whereas organic zinc and copper caused an increase in the elasticity and strength of the hairs and a simultaneous reduction in their diameter. It has been shown that the organic form of the supplemented trace zinc and copper (mainly copper) elements has a beneficial effect on the mechanical properties of the hairs since it results in an increase in both their elasticity and strength.

Changes in hair properties by Eucalyptus extract.

A long-term usage investigation of a scalp lotion containing Eucalyptus extract, which increases the amount of ceramide in the skin, was carried out to explore the change in physical properties of the hair fiber. Half-head or whole-head usage studies of a scalp lotion with Eucalyptus extract were carried out for the following groups: Japanese female, Japanese senior female, Japanese male, and Caucasian female panelists. As a result, the improvement in hair luster and bounce in the root part of the hair were recognized by the panelists after the long-term application of the scalp lotion with Eucalyptus extract. Measurement of hair gloss intensity and bending stress at the root suggests that this improvement is based on changes in these physical properties. These results indicate that the recognition of panelists is based on an actual change in the hair fiber properties. The efficacy of Eucalyptus extract is expressed regardless of race, age, or gender, since similar results were confirmed in all panelist groups. In order to investigate the cause of these phenomena, we measured the elasticity (Young's modulus) of the new-growth part of the cortex in Eucalyptus extract-treated hair and placebo hair by the nano-indentation method of atomic force microscopy (AFM). These results suggest that the Young's modulus of the new-growth part of the cortex in Eucalyptus extract treated-hair increases in comparison with placebo hair. The IR spectra of treated samples of hair show changes that appear to confirm a decrease in the alpha-helix structure and an increase in the beta-sheet structure.

Effect of oral intake of choline-stabilized orthosilicic acid on hair tensile strength and morphology in women with fine hair.

The appearance of hair plays an important role in people's overall physical appearance and self-perception. Silicon (Si) has been suggested to have a role in the formation of connective tissue and is present at 1-10 ppm in hair. Choline-stabilized orthosilicic acid ("ch-OSA") is a bioavailable form of silicon which was found to improve skin microrelief and skin mechanical properties in women with photoaged skin. The effect of ch-OSA on hair was investigated in a randomized, double blind, placebo-controlled study. Forty-eight women with fine hair were given 10 mg Si/day in the form of ch-OSA beadlets (n = 24) or a placebo (n = 24), orally for 9 months. Hair morphology and tensile properties were evaluated before and after treatment. Urinary silicon concentration increased significantly in the ch-OSA supplemented group but not in the placebo group. The elastic gradient decreased in both groups but the change was significantly smaller in the ch-OSA group (-4.52%) compared to placebo group (-11.9%). Break load changed significantly in the placebo group (-10.8%) but not in the ch-OSA supplemented group (-2.20%). Break stress and elastic modulus decreased in both groups but the change was smaller in the ch-OSA group. The cross sectional area increased significantly after 9 months compared to baseline in ch-OSA supplemented subjects but not in the placebo group. The change in urinary silicon excretion was significantly correlated with the change in cross sectional area. Oral intake of ch-OSA had a positive effect on tensile strength including elasticity and break load and resulted in thicker hair.

Hypothalamic thyroid hormone catabolism acts as a gatekeeper for the seasonal control of body weight and reproduction.

Seasonal adaptations in physiology exhibited by many animals involve an interface between biological timing and specific neuroendocrine systems, but the molecular basis of this interface is unknown. In this study of Siberian hamsters, we show that the availability of thyroid hormone within the hypothalamus is a key determinant of seasonal transitions. The expression of the gene encoding type III deiodinase (Dio3) and Dio3 activity in vivo (catabolism of T(4) and T(3)) is dynamically and temporally regulated by photoperiod, consistent with the loss of hypothalamic T(3) concentrations under short photoperiods. Chronic replacement of T(3) in the hypothalamus of male hamsters exposed to short photoperiods, thus bypassing synthetic or catabolic deiodinase enzymes located in cells of the ependyma of the third ventricle, prevented the onset of short-day physiology: hamsters maintained a long-day body weight phenotype and failed to undergo testicular and epididymal regression. However, pelage moult to a winter coat was not affected. Type II deiodinase gene expression was not regulated by photoperiod in these hamsters. Collectively, these data point to a pivotal role for hypothalamic DIO3 and T(3) catabolism in seasonal cycles of body weight and reproduction in mammals.

Blood vitamin concentrations in privately owned dogs fed non-standardized commercial diets and after intake of diets with specified vitamin concentrations.

The objective was to investigate in a survey study the blood vitamin concentrations in healthy dogs fed non-specified commercial complete diets and in an intervention study to determine the effects of defined dietary vitamin intakes on blood vitamin levels and hair and skin condition. Sixty-four privately owned dogs, aged from 1 to 8 years, without history of skin or coat problems were included. All animals were fed commercial complete diets with uncertain vitamin concentrations before enrolment. The animals were assigned, according to weight and gender, to four groups with graded vitamin intakes. The blood vitamin levels and skin and coat quality of the dogs were investigated at days 0 and day 122. Coat and hair condition was not influenced by the experimental diets. The retinol concentrations were reduced at the end of the experiment compared with the baseline levels, retinyl esters were not influenced. 25-Hydroxycholecalciferol decreased in all groups, alpha-tocopherol was constant or tended to decrease. Ascorbic acid, thiamine pyrophosphate and riboflavin concentrations were not affected by treatment, flavin adenine dinucleotide and pyridoxal-5'-phosphate were partially reduced on day 122. Cobalamin, pantothenate and biotin concentrations increased with higher dietary intakes, folate levels in tendency. In conclusion, this study gives a survey of blood vitamin concentrations in healthy dogs and provides a data base for the evaluation of the vitamin status in health and disease.

The thalamic intergeniculate leaflet mediates locomotor activity-induced reversal of phenotype in photoperiod nonresponsive Siberian hamsters.

The role of the intergeniculate leaflet of the thalamus (IGL) in photoperiod responsiveness was examined in a laboratory-selected line of photoperiod nonresponsive (NR) Siberian hamsters. NR hamsters fail to exhibit typical winter-type responses (i.e., gonadal regression and development of winter-type pelage) when exposed to short day lengths (e.g., 10 h of light/day). Earlier studies revealed that NR hamsters will exhibit winter-type responses when exposed to short photoperiod if they are given free access to a running wheel. The present study tested the hypothesis that this locomotor activity-induced reversal of phenotype is dependent on the IGL. Male NR hamsters underwent destruction of the IGL prior to being housed in short day lengths in cages equipped with running wheels. Activity rhythms were monitored for 8 weeks, after which time pelage response and paired testes weights were obtained. In contrast to sham-operated NR animals given access to running wheels, IGL-ablated animals showed no increase in the duration of nocturnal running wheel activity and became active later in the night than sham-lesioned animals. Lesioned animals also failed to exhibit the typical short photoperiod-induced gonadal regression and pelage molt. The results implicate the IGL in the mechanism by which running wheel activity can influence photoperiodic responses.