Nano-Neurotheranostics: Impact of Nanoparticles on Neural Dysfunctions and Strategies to Reduce Toxicity for Improved Efficacy

Nanotheranostics is one of the emerging research areas in the field of nanobiotechnology offering exciting promises for diagnosis, bio-separation, imaging mechanisms, hyperthermia, phototherapy, chemotherapy, drug delivery, gene delivery, among other uses. The major criteria for any nanotheranostic-materials is 1) to interact with proteins and cells without meddling with their basic activities, 2) to maintain their physical properties after surface modifications and 3) must be nontoxic. One of the challenging targets for nanotheranostics is the nervous system with major hindrances from the neurovascular units, the functional units of blood-brain barrier. As blood-brain barrier is crucial for protecting the CNS from toxins and metabolic fluctuations, most of the synthetic nanomaterials cannot pass through this barrier making it difficult for diagnosing or targeting the cells. Biodegradable nanoparticles show a promising role in this aspect. Certain neural pathologies have compromised barrier creating a path for most of the nanoparticles to enter into the cells. However, such carriers may pose a risk of side effects to non-neural tissues and their toxicity needs to be elucidated at preclinical levels. This article reviews about the different types of nanotheranostic strategies applied in nervous dysfunctions. Further, the side effects of these carriers are reviewed and appropriate methods to test the toxicity of such nano-carriers are suggested to improve the effectiveness of nano-carrier based diagnosis and treatments.

Neuroprosthesis Devices Based on Micro- and Nanosensors: A Systematic Review

Background. A neuroprosthesis (NP) is a medical device that compensates and restores functionality of neural dysfunctions affected by different pathologies and conditions. To this end, an implantable NP (INP) must monitor and electrically stimulate neuronal small structures in the peripheral and central nervous system. Therefore, one of the most important parts of INPs are the sensors and electrodes since their size, resolution, and material are key for their design and performance. Currently, most of the studies focus only on the INP application but do not show the technical considerations of the sensors. Objective. This paper is a systematic literature review that summarizes and synthesizes implantable micro- and nanosensors/electrodes used in INPs for sensing and stimulating tissues. Data Sources. Articles and patents published in English were searched from electronic databases. No restrictions were made in terms of country or journal. Study Selection. All reports related to sensors/electrodes applied in INPs were included, focusing on micro- and nanotechnologies. Main Outcome Measures. Performance and potential profit. Results. There was a total of 153 selected articles from the 2010 to June 2020 period, of which 16 were about cardiac pacemakers, 15 cochlear implants, 13 retinal prosthesis, 31 deep brain stimulation, 6 bladder implants, and 18 implantable motor NPs. All those INPs are used for support or recovery of neural functions for hearing, seeing, pacing, and motor control, as well as bladder and bowel control. Micro- and nanosensors for signal stimulation and recording have four special requirements to meet: biocompatibility, long-term reliability, high selectivity, and low-energy consumption. Current and future considerations in sensor/electrode design should focus on improving efficiency and safety. This review is a first approximation for those who work on INP design; it offers an idea of the complexity on the matter and can guide them to specific references on the subject.

The truth in social construction

Central strands of biological psychiatry, such as the Research Domain Criteria championed by Thomas Insel, aim to identify mental illnesses with genetic and/or neural dysfunctions. Such approaches are justified by the mismatch between psychopathologies picked out by descriptive criteria (such as those used by the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders) and neural correlates: patients presenting with the same symptoms may share little at the neural level, while those who share dysfunction at the neural level may exhibit quite different symptoms. Biological psychiatry is typically understood as opposed to social constructionist approaches to mental illness. This chapter argues that because symptomatology and disorders of neural circuits fail to match, biological psychiatry needs to embrace social construction, broadly understood. The differences at the level of symptomatology will often be explicable by differences in patients’ individual histories and social and cultural settings. The notion that social construction and biological psychiatry are mutually exclusive arises from an inchoate and incoherent feeling on both sides that only the second offers a physicalist explanation of mind and behaviour; in fact, a social explanation can ultimately be cashed out in physicalist terms. Nevertheless, systematicity of the kind sciences seek will need to be sought at the level of representations, as well as at the level of the brain, since cultural and social factors are unlikely to be able to be cashed out in terms of physical natural kinds.

Overview of the Cerebellar Function in Anticipatory Postural Adjustments and of the Compensatory Mechanisms Developing in Neural Dysfunctions

This review aims to highlight the important contribution of the cerebellum in the Anticipatory Postural Adjustments (APAs). These are unconscious muscular activities, accompanying every voluntary movement, which are crucial for optimizing motor performance by contrasting any destabilization of the whole body and of each single segment. Moreover, APAs are deeply involved in initiating the displacement of the center of mass in whole-body reaching movements or when starting gait. Here we present literature that illustrates how the peculiar abilities of the cerebellum i) to predict, and contrast in advance, the upcoming mechanical events; ii) to adapt motor outputs to the mechanical context, and iii) to control the temporal relationship between task-relevant events, are all exploited in the APA control. Moreover, recent papers are discussed which underline the key role of cerebellum ontogenesis in the correct maturation of APAs. Finally, on the basis of a survey of animal and human studies about cortical and subcortical compensatory processes that follow brain lesions, we propose a candidate neural network that could compensate for cerebellar deficits and suggest how to verify such a hypothesis.

Cumulative effects of social stress on reward-guided actions and prefrontal cortical activity

When exposed to chronic social stress, animals display behavioral changes that are relevant to depressive-like phenotypes. However, the cascading relationship between incremental stress exposure and neural dysfunctions over time remains incompletely understood. Here we characterize the longitudinal effect of social defeat on goal-directed actions and prefrontal cortical activity in mice, using a head-fixed sucrose preference task and two-photon calcium imaging. Behaviorally, stress-induced loss of reward sensitivity intensifies over days. Motivational anhedonia, the failure to translate positive reinforcements into future actions, requires multiple sessions of stress exposure to become fully established. For neural activity, individual layer 2/3 pyramidal neurons in the Cg1 and M2 subregions of the medial prefrontal cortex have heterogeneous responses to stress. Changes in ensemble activity differ significantly between susceptible and resilient animals after the first defeat session, and continue to diverge following successive stress episodes before reaching persistent abnormal levels. Collectively, these results demonstrate that the cumulative impact of an ethologically relevant stress can be observed at the level of cellular activity of individual prefrontal neurons. The distinct neural responses associated with resilience versus susceptibility raises the hypothesis that the negative impact of social stress is neutralized in resilient animals, in part through an adaptive reorganization of prefrontal cortical activity.

Neurobiology and Neuroimaging of PTSD

This chapter provides a broad overview of the fear circuitry implicated in the development and maintenance of posttraumatic stress disorder. It begins by reviewing evidence from animal models of fear conditioning and extinction that unveiled the neural structures incorporated in the fear circuitry. Then it explores the translation of these findings to healthy human models of fear conditioning and finally examines the neural dysfunctions highlighted by neuroimaging studies of posttraumatic stress disorder (PTSD) in order to conceptualize mechanisms of fear extinction and the role of impaired fear extinction in contributing to the pathology of PTSD. The chapter ends with the potential therapeutic interventions for the treatment of PTSD in the scope of this model but with a note of caution regarding some of its limitations.