RESUMO
The world faces two seemingly unrelated challenges-a shortfall in the STEM workforce and increasing antibiotic resistance among bacterial pathogens. We address these two challenges with Tiny Earth, an undergraduate research course that excites students about science and creates a pipeline for antibiotic discovery.
Assuntos
Antibacterianos , Descoberta de Drogas/educação , Ciência/educação , Estudantes , Bactérias/efeitos dos fármacos , Descoberta de Drogas/métodos , HumanosRESUMO
Many individuals with Parkinson disease (PD) have difficulty producing normal speech and voice, resulting in problems with interpersonal communication and reduced quality of life. Translational animal models of communicative dysfunction have been developed to assess disease pathology. However, it is unknown whether acoustic feature changes associated with vocal production deficits in these animal models lead to compromised communication. In rodents, male ultrasonic vocalizations (USVs) have a well-established role in functional inter-sexual communication. To test whether acoustic deficits in USVs observed in a PTEN-induced putative kinase 1 (PINK1) knockout (KO) PD rat model compromise communication, we presented recordings of male PINK1 KO USVs and normal wild-type (WT) USVs to female rat listeners. We measured approached behavior and immediate early gene expression (c-Fos) in brain regions implicated in auditory processing and sexual motivation. Our results suggest that females show reduced approach in response to PINK1 KO USVs compared with WT. Moreover, females exposed to PINK1 KO USVs had lower c-Fos immunolabeling in the nucleus accumbens, a region implicated in sexual motivation. These results are the first to demonstrate that vocalization deficits in a rat PD model result in compromised communication. Thus, the PINK1 KO PD model may be valuable for assessing treatments aimed at restoring vocal communicative function.
Assuntos
Percepção Auditiva/genética , Núcleo Accumbens/metabolismo , Doença de Parkinson/fisiopatologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Comportamento Social , Vocalização Animal/fisiologia , Estimulação Acústica , Animais , Modelos Animais de Doenças , Feminino , Masculino , Doença de Parkinson/genética , Jogos e Brinquedos/psicologia , Proteínas Quinases/deficiência , Proteínas Quinases/genética , Proteínas Proto-Oncogênicas c-fos/genética , Ratos , Ratos Long-Evans , Ratos Transgênicos , Espectrografia do Som , Estatísticas não Paramétricas , UltrassomRESUMO
Parkinson's disease (PD) is a progressive neurodegenerative disease that leads to a wide range of motor and nonmotor deficits. Specifically, voice and swallow deficits manifest early, are devastating to quality of life, and are difficult to treat with standard medical therapies. The pathological hallmarks of PD include accumulation of the presynaptic protein α-synuclein (αSyn) as well as degeneration of substantia nigra dopaminergic neurons. However, there is no clear understanding of how or when this pathology contributes to voice and swallow dysfunction in PD. The present study evaluates the effect of loss of function of the phosphatase and tensin homolog-induced putative kinase 1 gene in rats (PINK1(-/-) ), a model of autosomal recessive PD in humans, on vocalization, oromotor and limb function, and neurodegenerative pathologies. Behavioral measures include ultrasonic vocalizations, tongue force, biting, and gross motor performance that are assayed at 2, 4, 6, and 8 months of age. Aggregated αSyn and tyrosine hydroxylase immunoreactivity (TH-ir) were measured at 8 months. We show that, compared with wild-type controls, PINK1(-/-) rats develop (1) early and progressive vocalization and oromotor deficits, (2) reduced TH-ir in the locus coeruleus that correlates with vocal loudness and tongue force, and (3) αSyn neuropathology in brain regions important for cranial sensorimotor control. This novel approach of characterizing a PINK1(-/-) genetic model of PD provides the foundational work required to define behavioral biomarkers for the development of disease-modifying therapeutics for PD patients.
Assuntos
Ataxia/genética , Encéfalo/patologia , Doença de Parkinson/genética , Proteínas Quinases/genética , Vocalização Animal/fisiologia , Animais , Modelos Animais de Doenças , Técnicas de Inativação de Genes , Imuno-Histoquímica , Masculino , Atividade Motora/genética , Força Muscular/genética , Doença de Parkinson/complicações , Doença de Parkinson/patologia , Ratos , Ratos Long-Evans , Língua/inervação , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismoRESUMO
The steroid hormone testosterone (T) is a well-known mediator of male sexual behavior in vertebrates. However, less is known about T's rapid effects on sexual behavior, particularly those involving ultrasonic vocalizations (USVs), a mode of communication that can influence mate acquisition in rodents. Using the monogamous California mouse, Peromyscus californicus, we tested whether T rapidly alters male USV production by giving T or saline injections to non-paired (sexually naïve) males and paired (paternally experienced and pair-bonded) males immediately prior to a brief exposure to an unrelated, novel female. Among non-paired males, no differences in the total number of USVs were observed; however, T increased the proportion of simple sweeps produced. Among paired males, T decreased the number of USVs produced, and this change was driven by a reduction in simple sweeps. These results suggest a differential rapid effect of T pulses between non-paired and paired males upon exposure to a novel female. Additionally, we observed a positive correlation in the production of USVs made between males and novel females, and this relationship was altered by T. Given the importance of USVs in sexual communication, our study supports an essential concept of monogamy in that mate fidelity is reinforced by decreased responsiveness to prospective mates outside of the pair bond. The central mechanism in pair bonded males that decreases their responsiveness to novel females appears to be one that T can trigger. This is among the first studies to demonstrate that T can inhibit sexually related behaviors and do so rapidly.
Assuntos
Ligação do Par , Comportamento Sexual Animal/fisiologia , Testosterona/fisiologia , Vocalização Animal/fisiologia , Envelhecimento/psicologia , Comunicação Animal , Animais , Feminino , Masculino , Modelos Psicológicos , PeromyscusRESUMO
Most studies of mate choice have focused on female preference for male traits because it is generally assumed that since males provide less parental investment they are not choosy. However, if males suffer missed opportunity costs by mating with lower quality females, selection should favor males with the ability to discriminate among females. We tested the hypothesis that male house mice (Mus musculus) discriminate between females that differ in nutritional status (non-food-deprived versus food-deprived). We recorded the time males spent investigating either type of female and used that to determine preference (spending > or = 55% of their total investigation time with one female). We also examined the effects of female nutritional status and female preference status (preferred versus non-preferred) on the reproductive success of males. Males did not display a preference for non-food-deprived females nor did their reproductive success vary with nutritional status or preference status of females. Interestingly, males spent more time investigating females that were closest to the male's own weight. In addition, pairs that were closer in weight were more likely to produce a litter. These results suggest that male house mice are capable of discriminating among females and that such discrimination may influence their reproductive success.